Information on EC 3.1.4.35 - 3',5'-cyclic-GMP phosphodiesterase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
3.1.4.35
-
RECOMMENDED NAME
GeneOntology No.
3',5'-cyclic-GMP phosphodiesterase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
guanosine 3',5'-cyclic phosphate + H2O = GMP
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-GMP 5'-nucleotidohydrolase
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3',5'-cyclic GMP phosphodiesterase
-
-
-
-
cGMP phosphodiesterase
-
-
-
-
cGMP-PDE
-
-
-
-
cyclic 3',5'-GMP phosphodiesterase
-
-
-
-
cyclic GMP phosphodiesterase
-
-
-
-
cyclic guanosine 3',5'-monophosphate phosphodiesterase
-
-
-
-
cyclic guanosine 3',5'-phosphate phosphodiesterase
-
-
-
-
guanosine cyclic 3',5'-phosphate phosphodiesterase
-
-
-
-
phosphodiesterase cGMP
-
-
-
-
phosphodiesterase, guanosine cyclic 3',5'-phosphate
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9068-52-4
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
silkworm
-
-
Manually annotated by BRENDA team
isoform PDE5
-
-
Manually annotated by BRENDA team
isoform PDE6
-
-
Manually annotated by BRENDA team
methods of enzyme determination
-
-
Manually annotated by BRENDA team
PDE6
-
-
Manually annotated by BRENDA team
Bos taurus PDE6
PDE6
-
-
Manually annotated by BRENDA team
strains AX3 and DH1
-
-
Manually annotated by BRENDA team
isoforms PDE5, PDE6
-
-
Manually annotated by BRENDA team
strains NC4, XP55 and NP377
SwissProt
Manually annotated by BRENDA team
generation of transgenic animals with targeted expression of DmPDE6 to tubule type I (principal) cells. This reveals localization of DmPDE6 primarily at the apical membranes. Overexpression of DmPDE6 results in elevated cG-PDE activity and decreased tubule cGMP content. Such targeted overexpression of DmPDE6 creates a novel phenotype that manifests itself in inhibition of the active transport and efflux of cGMP by tubules
-
-
Manually annotated by BRENDA team
; isoform PDE5
-
-
Manually annotated by BRENDA team
isoenzymes PDE5A1, PDE5A2 and PDE5A3
-
-
Manually annotated by BRENDA team
isoform PDE5
-
-
Manually annotated by BRENDA team
isoform PDE5A
SwissProt
Manually annotated by BRENDA team
isoform PDE5A1
SwissProt
Manually annotated by BRENDA team
isoform PDE6
-
-
Manually annotated by BRENDA team
isoforms PDE5, three splice variants: PDE5A1, PDE5A2, PDE5A3. Enzyme promoters are sensitive to cGMP or cAMP stimulation
-
-
Manually annotated by BRENDA team
PDE5; PDE9
-
-
Manually annotated by BRENDA team
PDE5A
SwissProt
Manually annotated by BRENDA team
PDE9A
SwissProt
Manually annotated by BRENDA team
recombinant and native
-
-
Manually annotated by BRENDA team
recombinant PDE5A1
-
-
Manually annotated by BRENDA team
splice variants PDE5A1 and PDE5A2
SwissProt
Manually annotated by BRENDA team
splice variants PDE9A5 and PDE9A1
SwissProt
Manually annotated by BRENDA team
isoform PDE6
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
no activity in Homo sapiens
functional PDE6 not detected in Y79 retinoblastoma cells. Attempts to enhance iexpression with cell culture or with introduction of virus expressing PDE6 are not successful. The results indicate that expression of a fully active stable PDE6 enzyme requires other post-transcriptional events that do not occur or are inhibited in Y79 cells
-
-
Manually annotated by BRENDA team
isoform PDE5
-
-
Manually annotated by BRENDA team
frog
-
-
Manually annotated by BRENDA team
isoforms PDE5, PDE9
UniProt
Manually annotated by BRENDA team
pregnant rat
-
-
Manually annotated by BRENDA team
spontaneous hypertensive rats
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
mechanisms for PDE activation are similar in mammalian and amphibian photoreceptors as well as in rods and cones
malfunction
-
chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular myocardial remodeling
malfunction
-
disruption of the cyclic nucleotide phosphodiesterase PDEdelta gene causes significantly reduced cGMP-PDE activity and greatly reduced ability to undergo gametogenesis
malfunction
-
enhanced cGMP-dependent protein kinase activity by PDE5 inhibition negatively regulates ERK1/2 activity. PDE5 inhibition suppresses serotonin signalling and consequent cellular proliferation in primary cultured pulmonary artery smooth muscle cells
malfunction
-
inhibition of cGMP phosphodiesterase 5 suppresses matrix metalloproteinase-2 production in pulmonary artery smooth muscle cells
malfunction
-
inhibition of PDE-5 slows cGMP degradation, leading to increased levels of cGMP and greater blood flow through the corpus cavernosum when nitric oxide is released during sexual stimulation, PDE-5 inhibitors have little effect on corpus cavernosum blood flow
malfunction
-
PDE5 inhibitors may elevate the expression of nNOS by relaxing the smooth muscle of the ureteral wall through suppression of fibrosis
malfunction
-
decreasing effect of PDE5 inhibition on vascular contractility, overview
malfunction
-
identification of a Pgamma-depleted PDE as Palphabetagamma, detailed overview
malfunction
Rattus norvegicus Sprague-Dawley
-
decreasing effect of PDE5 inhibition on vascular contractility, overview
-
metabolism
-
modulation of the NO-cGMP pathway using the PDE-5 inhibitor zaprinast alters the display of paced mating behaviors in rats
metabolism
-
during rod phototransduction, cGMP and Ca2+ are regulated by PDE6, guanylate cyclase, and cGMP-gated Na+/Ca2+ channels. The level of cGMP is controlled by opposing activities of PDE6 and guanylate cyclase and, at sufficiently high levels, Na+/Ca2+ channels open to allow increased Ca2+ influx into the rod outer segment
metabolism
Mus musculus C57BL/6J
-
during rod phototransduction, cGMP and Ca2+ are regulated by PDE6, guanylate cyclase, and cGMP-gated Na+/Ca2+ channels. The level of cGMP is controlled by opposing activities of PDE6 and guanylate cyclase and, at sufficiently high levels, Na+/Ca2+ channels open to allow increased Ca2+ influx into the rod outer segment
-
physiological function
-
PDEdelta plays a crucial role in regulating cGMP levels during sexual development
physiological function
-
cyclic GMP phosphodiesterase in bovine rod photoreceptor outer segments comprises a catalytic subunit complex, Palphabeta, and two inhibitory subunits Pgamma, and is regulated by the a subunit of transducin. The mechanism for PDE regulation involves complex formations between the gamma subunits with outer segments, overview. Pgamma as a complex with the GTP-bound transducin a subunit, GTP-Talpha, dissociates from Palphabetagammagamma on membranes, and the Palphabetagammagamma becomes Pgamma-depleted
physiological function
-
PDE6 consistis of catalytic alpha and beta subunits and two inhibitory gamma subunits, molecular mechanism of PDE6gamma regulation of the catalytic subunits, overview. Ile86 and Ile87 residues are necessary for normal inhibition of PDE6 catalytic activity in vivo, and increased basal activity of PDE can be partially compensated by GCAP-dependent regulation of guanylyl cyclase
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-O-anthraniloyl cGMP + H2O
2'-O-anthraniloyl GMP
show the reaction diagram
-
-
-
?
2'-O-anthraniloyl-cGMP + H2O
?
show the reaction diagram
-
phosphorylation increases affinity for hydrolysis of 2'-O-anthraniloyl-cGMP by about 3fold
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
-
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
P52731
very low activity
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Bos taurus, Bos taurus PDE6
-
activity with 3',5'-cAMP is higher than with 3',5'-cGMP, PDE6
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
P52731
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
Q864F1
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
allosteric cGMP-binding sites of PDE5 could regulate cGMP signaling by sequestering cGMP from cGMP-dependent protein kinase and perhaps from the PDE5 catalytic site as well. The cGMP sequestered by binding of cGMP to PDE5 R domain significantly dampens activation of cGMP-dependent protein kinase and hydrolysis of cGMP by PDE5 C domain
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
suPDE5 regulates cGMP levels in sperm, which in turn modulate sperm motility
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
activity with 3',5'-cAMP is higher than with 3',5'-cGMP, PDE6
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE5A1
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
selective for 3',5'-cGMP, PDE9
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
specific for 3',5'-cGMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
specific for 3',5'-cGMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
specific for 3',5'-cGMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
Q2V2M6
specific for 3',5'-cGMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
specific for 3',5'-cGMP, no activity with 3',5'-cAMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
O76074
PDE5 hydrolyses selectively 3',5'-cGMP with high affinity
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE5 is specific for cGMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
Q8CG03
PDE5A has a higher selectivity for cGMP due to much lower cAMP binding affinity
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE5 and PDE6 show specificity for cGMP relative to cAMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE5 is cGMP-specific
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
O54735
PDE5 specifically targets 3',5'-cyclic GMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE6 shows specificity for cGMP relative to cAMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
Bos taurus PDE6
-
activity with 3',5'-cAMP is higher than with 3',5'-cGMP, PDE6
-
-
?
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
phosphodiesterase 5 converts the second messenger 3',5'-cGMP to its inactive form
-
-
?
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
PDE5
-
-
?
cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
cGMP + H2O
5'-GMP
show the reaction diagram
O76074
-
-
-
?
cGMP + H2O
5'-GMP
show the reaction diagram
-
degradation of intracellular cGMP
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O76074
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O76074
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Q8MLZ3
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Q8QZV1
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O70628
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Q8UUY2, Q8UUY6, Q8UUY7
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O76083
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
very low activity with cAMP
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
?
additional information
?
-
-
human chorionic gonadotropin reduces PDE5 expression and enzyme activity in smooth muscle cells, possibly through a pathway involving cAMP
-
-
-
additional information
?
-
-
in mammals the enzyme might play key roles in the aquisition and maintenance of the myoid cell contractile phenotype and more generally in the testis maturation
-
-
-
additional information
?
-
-
kinetics of a cellular nitric oxide/cGMP/phosphodiesterase-5 pathway
-
-
-
additional information
?
-
-
PDE5 controls the soluble but not the particulate pool of cGMP in rat cardiomyocytes
-
-
-
additional information
?
-
-
PDE5 gene expression and activity are androgen-dependent in vas deferens
-
-
-
additional information
?
-
-
PDE5 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
-
additional information
?
-
-
PDE5 may be involved in the cyclic nucleotide-mediated control of smooth muscle tone
-
-
-
additional information
?
-
-
PDE5 regulation of cGMP intracellular levels is not involved in the control of progression of smooth muscle cell cycle, but may represent one of the markers of the contractile phenotype
-
-
-
additional information
?
-
-
role for cG-PDE in modulating cGMP transport and efflux
-
-
-
additional information
?
-
O54735
cGMP levels in the spinal cord are controlled by a number of enzyme isoforms, that can be present in the same cell. Role of NO-cGMP signaling in nociceptive processing
-
-
-
additional information
?
-
-
isoform PDE5 regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling
-
-
-
additional information
?
-
-
isoform PDE5 regulation of cGMP intracellular levels is not involved in the control of smooth muscle cell cycle progression, but may represent one of the markers of the contractile phenotype
-
-
-
additional information
?
-
-
preincubation with cGMP increases catalytic activity for cGMP degradation, thus elevated cellular cGMP initiates a physiological negative feedback on the cGMP pathway by increasing the affinity of the PDE5 catalytic site for cGMP
-
-
-
additional information
?
-
-
PDE6 contains two regulatory GAF domains, of which one (GAF A) binds cGMP and regulates the activity of the PDE6 holoenzyme
-
-
-
additional information
?
-
-
prenylation of the enzyme is required for plasma-membrane targeting
-
-
-
additional information
?
-
-
tadalafil is not degraded by PDE5
-
-
-
additional information
?
-
-
analysis of diverse complxes formed by subunits Pgamma with GTP or GDP and outer segments, the complexes are extracted from membranes and isolated. Analysis of the function of the single complexes in PDE regulation, overview
-
-
-
additional information
?
-
-
interaction between the PDE6 gamma subunit with tubulin alpha and beta, specificity and mechanism, detailed overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
allosteric cGMP-binding sites of PDE5 could regulate cGMP signaling by sequestering cGMP from cGMP-dependent protein kinase and perhaps from the PDE5 catalytic site as well. The cGMP sequestered by binding of cGMP to PDE5 R domain significantly dampens activation of cGMP-dependent protein kinase and hydrolysis of cGMP by PDE5 C domain
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
suPDE5 regulates cGMP levels in sperm, which in turn modulate sperm motility
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE5 and PDE6 show specificity for cGMP relative to cAMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE5 is cGMP-specific
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
O54735
PDE5 specifically targets 3',5'-cyclic GMP
-
-
?
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
phosphodiesterase 5 converts the second messenger 3',5'-cGMP to its inactive form
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O76074
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O76074
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Q8MLZ3
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Q8QZV1
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O70628
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Q8UUY2, Q8UUY6, Q8UUY7
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O76083
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
very low activity with cAMP
-
?
additional information
?
-
-
human chorionic gonadotropin reduces PDE5 expression and enzyme activity in smooth muscle cells, possibly through a pathway involving cAMP
-
-
-
additional information
?
-
-
in mammals the enzyme might play key roles in the aquisition and maintenance of the myoid cell contractile phenotype and more generally in the testis maturation
-
-
-
additional information
?
-
-
kinetics of a cellular nitric oxide/cGMP/phosphodiesterase-5 pathway
-
-
-
additional information
?
-
-
PDE5 controls the soluble but not the particulate pool of cGMP in rat cardiomyocytes
-
-
-
additional information
?
-
-
PDE5 gene expression and activity are androgen-dependent in vas deferens
-
-
-
additional information
?
-
-
PDE5 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
-
additional information
?
-
-
PDE5 may be involved in the cyclic nucleotide-mediated control of smooth muscle tone
-
-
-
additional information
?
-
-
PDE5 regulation of cGMP intracellular levels is not involved in the control of progression of smooth muscle cell cycle, but may represent one of the markers of the contractile phenotype
-
-
-
additional information
?
-
-
role for cG-PDE in modulating cGMP transport and efflux
-
-
-
additional information
?
-
O54735
cGMP levels in the spinal cord are controlled by a number of enzyme isoforms, that can be present in the same cell. Role of NO-cGMP signaling in nociceptive processing
-
-
-
additional information
?
-
-
isoform PDE5 regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling
-
-
-
additional information
?
-
-
isoform PDE5 regulation of cGMP intracellular levels is not involved in the control of smooth muscle cell cycle progression, but may represent one of the markers of the contractile phenotype
-
-
-
additional information
?
-
-
preincubation with cGMP increases catalytic activity for cGMP degradation, thus elevated cellular cGMP initiates a physiological negative feedback on the cGMP pathway by increasing the affinity of the PDE5 catalytic site for cGMP
-
-
-
additional information
?
-
-
PDE6 contains two regulatory GAF domains, of which one (GAF A) binds cGMP and regulates the activity of the PDE6 holoenzyme
-
-
-
additional information
?
-
-
prenylation of the enzyme is required for plasma-membrane targeting
-
-
-
additional information
?
-
-
analysis of diverse complxes formed by subunits Pgamma with GTP or GDP and outer segments, the complexes are extracted from membranes and isolated. Analysis of the function of the single complexes in PDE regulation, overview
-
-
-
additional information
?
-
-
interaction between the PDE6 gamma subunit with tubulin alpha and beta, specificity and mechanism, detailed overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
activatory at 0.1-1 mM
Ca2+
-
required
Ca2+
-
Ca2+-dependent regulation of the enzyme by S-modulin
Ca2+
O76083
slight activation of PDE9A1
Ca2+
Q2V2M6
less active activator than Mn2+
Mg2+
-
5 mM activates
Mg2+
-
dependent
Mg2+
-
required for activity, maximal activity at 3-10 mM MgCl2
Mg2+
-
approx. 3fold increase in activity at 10 mM
Mg2+
O76083
required for activity, maximal activity at approx. 10 mM
Mg2+
-
required for activity, approx. 2fold activation at 1 mM
Mg2+
-
required for activity, approx. 2.5fold activation at 1 mM
Mg2+
-
required for activity, approx. 1.5fold activation at 1 mM
Mg2+
Q2V2M6
less active activator than Mn2+
Mn2+
-
2 mM activates
Mn2+
-
required
Mn2+
-
approx. 2.5fold higher activation than with Mg2+, maximal activity at 3-10 mM Mn2+
Mn2+
-
approx. 5fold increase in activity at 10 mM
Mn2+
O76083
required for activity, maximal activity at approx. 10 mM
Zn2+
-
slight activation at 0.01 mM, strong inhibition above
Zn2+
-
approx. 2.5 fold activation at 0.01 mM, strong inhibition above
Mn2+
Q2V2M6
more potent activator of PfPDE1 than Mg2+ and Ca2+ at concentrations of 0.01-10 mM, maximal activity at 1 mM MnCl2
additional information
Q8MLZ3
Zn+-binding motif
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0121 mM, PDE5
(2Z)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
-
IC50: 0.00067 mM, PDE5
(4-(4-[2-ethyl-phenylamino)-methylene]-3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl)-benzoic acid
-
0.00001 mM, 50% inhibition
(E)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone O-carbamoyl oxime
-
filaminast
1,2-dihydro-2-[(2-methyl-4-pyridinyl)methyl]-1-oxo-8-(2-pyrimidinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride
-
specific inhibitor of PDE5
1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
-
-
1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazol[3,4d]-pyrimidin-4-(5H)-one
-
0.000006 mM, 50% inhibition in sham operated rats
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
i.e. BAY 73-6691, IC50: 55 nM
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
i.e. BAY 73-6691, IC50: 100 nM
1-(2-ethoxyethyl)-3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
1-(2-ethoxyethyl)-3-methyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
1-(3-chloro-4-methoxybenzyl)-3-(cis-4-hydroxycyclohexyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-carbonitrile
-
-
1-[4-[(1,3-benzodioxol-5-ylmethyl)amino]-6-chloroquinazolin-2-yl]piperidine-4-carboxylic acid
-
-
1-[9-[(3-chloro-4-methoxybenzyl)amino]-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl]piperidin-4-ol
-
-
1-[9-[(3-chloro-4-methoxybenzyl)amino]-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl]piperidine-4-carboxylic acid
-
-
1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate
-
trivial name sildenafil citrate or Viagra
2',3'-cGMP
-
-
2,2',2'',2'''-[(4,8-dipiperidin-1-ylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
-
-
2-(2,4-dihydroxyphenyl)-8-[5-hydroxy-5-methyl-2-(1-methylethenyl)hexyl]-5-methoxy-4H-chromene-3,7-diol
-
-
2-(2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
-
-
2-(2-methylpyridin-4-yl)methyl-4-(3,4,5-trimethoxyphenyl)-8-(pyrimidin-2-yl)methoxy-1,2-dihydro-1-oxo-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride
-
i.e. T-0156, IC50: 0.23 mM, potent and highly selective phosphodiesterase type 5 inhibitor
2-(2-propoxyphenyl)-1,7-dihydro-6H-purin-6-one
-
-
2-(5-amino-2-propoxyphenyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-(5-[[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl]-2-propoxyphenyl)-5-methylquinazolin-4(3H)-one
-
-
2-bromo-5-ethyl-7,8-dihydro-1-[(4-hydroxyphenyl)methyl]-7(R)-(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0027 mM, PDE5
2-methoxy-7-methyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazin-6(5H)-one
-
-
2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one
-
trivial name vardenafil or Levitra
2-[2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl]-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
-
vardenafil
3',5'-cAMP
-
-
3',5'-cAMP
-
-
3',5'-cAMP
-
-
3',5'-cAMP
-
20% inhibition at 0.1 mM, 50% inhibition at 1 mM
3',5'-cIMP
-
-
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
-
-
3-(4-ethylpiperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-(cyclopentylmethoxy)-N-(2,6-dichlorophenyl)-4-methoxybenzamide
-
piclamilast
3-(cyclopropylmethoxy)-N-(2,6-dichlorophenyl)-4-(difluoromethoxy)benzamide
-
roflumilast
3-([2-[(2-hydroxyethyl)amino]ethyl]amino)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-ethyl-5-(4-methyl-1,4-diazepan-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(morpholin-4-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-1-(2-propoxyethyl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-1-[2-(propan-2-yloxy)ethyl]-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N-(4-fluorophenyl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N5-(1-methylpiperidin-4-yl)-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
-
-
3-isobutyl-1-methyl-8-methoxymethylxanthine
-
-
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
-
0.06 mM, 50% inhibition
3-isobutyl-1-methylxanthine
-
0.0058 mM, 50% inhibition
3-isobutyl-1-methylxanthine
-
0.0054 mM, 50% inhibition
3-isobutyl-1-methylxanthine
-
the inhibitor binds to a subpocket that comprises key residues Val782, Ph2786, Gln817 and Phe820 of PDE5A1. This subpocket may be a common site for binding nonselective inhibitors
3-isobutyl-1-methylxanthine
-
IC50: 0.032 mM
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
Q864F1
;
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
-
IBMX, a PDE6 inhibitor
3-methyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-methyl-5-[(3S)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-methyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-methyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-[(1R,4R)-2,5-diazabicyclo[2.2.1]hept-2-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[(2-aminoethyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[(6-deoxy-alpha-L-mannopyranosyl)oxy]-5-hydroxy-8-(1-hydroxy-2-methylprop-2-en-1-yl)-2-(4-methoxyphenyl)-4-oxo-3,4-dihydro-2H-chromen-7-yl beta-D-glucopyranoside
-
-
3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-(2,2-dihydroxypropyl)-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]-pyrazin-2(1H)-one
-
-
3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5
3-[4-(3-hydroxypropyl)-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-(3-hydroxypropyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-[(2R)-2-hydroxypropyl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-[(2R,3R)-3-hydroxybutan-2-yl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-[(2S)-2-hydroxypropyl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
3-[4-[(2S,3R)-3-hydroxybutan-2-yl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
4-(1,3-benzodioxol-5-ylmethoxy)-2-(1H-imidazol-1-yl)-5-phenylpyrimidine
-
-
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
-
Ro20-1724
4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylic acid
-
cilomilast
4-[3-ethyl-7-(pyrimidin-4-ylamino)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazin-2-one
-
-
4-[7-hydroxy-8-[5-hydroxy-5-methyl-2-(1-methylethenyl)hexyl]-5-methoxy-4H-chromen-2-yl]benzene-1,3-diol
-
-
5-(1,4-diazepan-1-yl)-3-ethyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
5-(1,4-diazepan-1-yl)-3-methyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
5-(2-propoxyphenyl)-2,3-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
5-(2-propoxyphenyl)-3,6-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
zardaverine
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0025 mM, PDE5
6-benzo[1,3]dioxol-5-yl-2-methyl-2,3,6,7,12,12a-hexahydropyrazinol[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
-
trivial name tadalafil or Cialis
6-deoxy-3-O-[6-deoxy-4-O-[7-(beta-D-glucopyranosyloxy)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-8-(2-methylprop-1-en-1-yl)-4-oxo-3,4-dihydro-2H-chromen-3-yl]-alpha-L-mannopyranosyl]-alpha-L-mannopyranose
-
-
7-(6-methoxypyridin-3-yl)-3-(piperazin-1-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
-
8-(5-[[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]sulfonyl]-2-propoxyphenyl)-6-propyl-6,6a,9,9a-tetrahydro-5H-[1,2,4]triazolo[3,4-i]purin-5-one
-
-
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
-
-
8-methoxymethyl-isobutylmethylxanthine
-
; inhibits isoform PDE5, is 3times more potent in inhibiting PDE5 than PDE1
9-[(3-chloro-4-methoxybenzyl)amino]-3-ethyl-N-methyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazine-6-carboxamide
-
-
amentoflavone
-
IC50: 0.0117 mM
amrinone
-
IC50: 0.2296 mM, PDE5
ATP
-
slight inhibition at 1 mM
avanafil
-
TA-1790, highly selective inhibitor of PDE5
BAY 60-7550
-
-
BAY 73-6691
-
specific PDE9A inhibitor
benzamidenafil
-
i.e. N-(3,4-dimethoxy benzyl)-2-[[(1R,S)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide, potent and specific inhibitor of PDE-5
bilobetin
-
IC50: 0.00152 mM
Ca2+
-
inhibitory at 1 mM together with Mg2+ below 0.1 mM
Caffeine
-
-
Caffeine
-
-
cAMP
-
inhibition at high concentrations
cGMP
-
inhibition above 0.001 mM
chamomile
-
weak, but still statistically significant inhibition of PDE5A1
Cilostamide
-
-
Cilostamide
-
IC50: 0.0152 mM, PDE5
Cilostamide
-
IC50: 0.006 mM, PDE5
cilostazol
-
IC50: 0.0044 mM, PDE5
Colchicine
-
-
cone Pgamma subunit
-
PDE6C is potently inhibited by the recombinant cone and rod Pgamma-subunits with slight selectivity for the cone Pgamma
-
CP461
-
-
delphinidin
-
-
delphinidin 3-glucoside
-
-
dibutyryl 3',5'-cAMP
-
-
dioclein
-
dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 11fold more selective for the activated PDE1 isoform compared to PDE5 (16fold)
diosmetin
-
IC50: 0.015 mM, PDB5
dipyridamole
-
-
dipyridamole
-
IC50: 0.00026 mM, PDE5
dipyridamole
-
0.0013 mM, 50% inhibition
dipyridamole
-
0.00075 mM, 50% inhibition
dipyridamole
-
0.0012 mM, 50% inhibition
dipyridamole
Q2V2M6
IC50: 0.022 mM
dipyridamole
-
IC50: 0.023 mM
dipyridamole
-
PDE5 is specifically inhibited by dipyridamole
E4021
Q2V2M6
IC50: 0.046 mM
EDTA
-
completely inhibits at 10 mM
EDTA
-
-
EDTA
O76083
0.5 mM, 35% inhibition of activity in the absence of a divalent metal ion
Evo48
-
potent inhibitor of PDE5
-
exisulind
-
-
fructose 1,6-bisphosphate
-
-
fructose 6-phosphate
-
-
genistein
-
IC50: 0.073 mM, PDB5
ginkgetin
-
IC50: 0.00059 mM
GTP
-
slight inhibition at 1 mM
histone
-
-
Inhibitor protein
-
-
-
Inhibitor protein
-
gamma-subunit of enzyme
-
Inhibitor protein
-
gamma-subunit of enzyme; inhibitory in the dark
-
Inhibitor protein
-
-
-
Inhibitor protein
-
gamma-subunit of enzyme
-
inhibitory gamma subunit of PDE
-
i.e. Pgamma
-
luteolin
-
IC50: 0.0193 mM, PDB5
malvidin
-
IC50: 0.0354 mM
malvidin-3-O-beta-glucoside
-
IC50: 0.0116 mM
Mg2+
-
inhibitory below 0.1 mM together with Ca2+ at 1 mM
MY-5445
-
inhibition significantly increases contractility in hypertrophied myocardium
N-(3-chloro-4-methoxybenzyl)-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine
-
-
N-(3-chloro-4-methoxybenzyl)-3-ethyl-6-(pyridin-4-ylmethyl)-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-9-amine
-
-
N-[3-(1,3-dimethyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-propoxyphenyl]methanesulfonamide
-
-
N-[3-(4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]piperidine-1-carboxamide
-
-
N-[3-(4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]morpholine-4-carboxamide
-
-
N5-(2-aminoethyl)-3-ethyl-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
-
-
papaverine
-
-
Pb2+
-
-
peonidin
-
-
peonidin 3-glucoside
-
-
petunidin
-
-
petunidin 3-glucoside
-
-
PF-3717842
O54735
high-affinity phosphodiesterase-5 inhibitor
PF-4540124
O54735
-
Pgamma-inhibitory peptide
-
-
-
Pgamma-inhibitory peptide Pgamma63-87
-
-
-
Pgamma-inhibitory peptide Pgamma70-87
-
-
-
PgammaPDE6
Q8UUY2, Q8UUY6, Q8UUY7
regulatory subunit of PDE6, inhibition of catalytic activity
-
Phosphate buffer
-
-
-
quercetin-3,5,7,3',4'-O-pentamethylether
-
-
quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate
-
-
quercetin-3-O-methylether
-
-
quinazolinamine
-
IC50: 0.000021 mM, PDE5
rod Pgamma subunit
-
PDE6C is potently inhibited by the recombinant cone and rod Pgamma-subunits with slight selectivity for the cone Pgamma
-
rolipram
-
-
rolipram
-
-
rolipram
-
-
RP-73401
-
IC50: 0.0089 mM, PDE5
SCH 51866
O76083
0.0029 mM, 50% inhibition of PDE9A5, 0.0033 mM, 50% inhibition of PDE9A1
sciadopitysin
-
IC50: 0.00324 mM
sequoiaflavone
-
IC50: 0.0199 mM
sildenafil
-
0.0000035 mM, 50% inhibition
sildenafil
O76083
0.011 mM, 50% inhibition of PDE9A5, 0.008 mM, 50% inhibition of PDE9A1
sildenafil
-
0.0000017 mM, 50% inhibition
sildenafil
-
0.0000036 mM, 50% inhibition
sildenafil
-
0.000003 mM, 50% inhibition
sildenafil
-
pharmacologic inhibition of PDE5 in uterus blunts myometrical contractility during active labor without a significant cardiovascular effect. Potential role for sildenafil as an adjunct for the treatment of preterm labor
sildenafil
-
IC50: IC50: 0.000025 mM
sildenafil
Q2V2M6
IC50: 0.056 mM
sildenafil
-
IC50: 3.6 nM
sildenafil
-
IC50: 49 nM, PDE6
sildenafil
-
IC50: 8.5 nM, PDE5; IC50: above 10000 nM, PDE9
sildenafil
-
IC50: 3.7 nM, 1000fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
sildenafil
-
IC50: 0.005 mM
sildenafil
-
IC50: 7.8 nM
sildenafil
-
IC50: 3.7 nM
sildenafil
-
nerve-induced relaxation of urethral preparations are enhanced at low concentrations of sildenafil, with direct smooth muscle-relaxant actions of the inhibitors at high concentrations
sildenafil
-
inhibition significantly increases contractility in hypertrophied myocardium
sildenafil
-
binding to the active site
sildenafil
-
blocking of 70% of total cGMP hydrolizing activity
sildenafil
-
preincubation with cGMP increases catalytic activity for cGMP degradation, but also for binding of inhibitor
sildenafil
Q864F1
0.01 mM sildenafil inhibits 84% and 68% of the activity measured in detergent-resistant membranes and detergent-soluble fractions, respectively; 0.01 mM sildenafil inhibits 84% and 68% of the activity measured in detergent-resistant membranes and detergent-soluble fractions, respectively
sildenafil
-
70% inhibition at 100 nM
sildenafil
Q8CG03
potent PDE5 inhibitor
sildenafil
-
potent competitive inhibitor of phosphodiesterase 5
sildenafil
O54735
UK-92,480, trade name Viagra
sildenafil
-
commercial name Viagra
sildenafil
-
selective PDE5 inhibitor
sildenafil
-
PDE5 inhibitor
sildenafil
-
-
sildenafil
-
potent inhibitor of phosphodiesterase-5
sildenafil
-
high sensitivity of PDE5 for sildenafil can be obtained through cGMP-induced activation of PDE or through cGMP-independent modulation of PDE5 in the nonactivated state
sildenafil
-
specific PDE5 inhibitor
sildenafil
-
a PDE5 inhibitor, reduces phenylephrine-induced maximal contraction similarly in angiotensin II and control rats
sildenafil citrate
O76074
inhibition of PDE5 activity in the intestine, which might occur during sildenafil citrate ingestion, could result in a transitory diarrhoe
SLx-2101
-
inhibits excellent potency both ex vivo and in vivo
Sodium deoxycholate
-
-
T-1032
-
IC50: 0.041 mM
T0156
-
selective phosphodiesterase type 5 inhibitor
tadalafil
-
IC50: 9.4 nM, PDE5; IC50: above 10000 nM, PDE9
tadalafil
-
IC50: 1.8 nM, 40fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
tadalafil
-
IC50: 1.8 nM
tadalafil
-
nerve-induced relaxation of urethral preparations are enhanced at low concentrations of tadalafil, with direct smooth muscle-relaxant actions of the inhibitors at high concentrations
tadalafil
-
blocking of 70% of total cGMP hydrolizing activity
tadalafil
-
preincubation with cGMP increases catalytic activity for cGMP degradation, but also for binding of inhibitor
tadalafil
Q8CG03
potent PDE5 inhibitor
tadalafil
-
cGMP modestly but significantly increases the affinity of PDE5 for tadalafil by 1.7fold
tadalafil
-
commercial name Cialis
tadalafil
-
-
theophylline
-
-
theophylline
-
-
theophylline
-
-
trans-4-([2-[(3-chloro-4-methoxyphenyl)carbamoyl]-4-cyanophenyl]carbamoyl)cyclohexanecarboxylic acid
-
-
udenafil
-
trade name Zydena, a PDE5 inhibitor developed as a medical treatment for erectile dysfunction
udenafil
-
DA-8159 or Zydena, potent PDE5 inhibitor
UK-369,003
-
i.e. 1-[6-ethoxy-5-[3-ethyl-6,7-dihydro-2-(2-methoxyethyl)-7-oxo-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-pyridyl sulfonyl]-4-ethylpiperazine benzenesulfonate, a potent selective inhibitor of cGMP-specific PDE5 with more than 80fold selectivity for PDE5 over PDE6, more than 3000fold selectivity over PDEs 1-4 and 10, and more than 10000fold selectivity over PDE11
vardenafil
-
IC50: 11 nM, PDE6
vardenafil
-
IC50: 0.89 nM, PDE5; IC50: 3370 nM, PDE9
vardenafil
-
IC50: 0.091 nM, 9300fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
vardenafil
-
IC50: 0.091 nM
vardenafil
-
nerve-induced relaxation of urethral preparations are enhanced at low concentrations of vardenafil, with direct smooth muscle-relaxant actions of the inhibitors at high concentrations
vardenafil
-
blocking of 70% of total cGMP hydrolizing activity. Blocking of enzyme with vardenafil increases the antiproliferative and relaxant effect of sodium nitroprusside on cells, which is almost ineffective in presence of active enzyme
vardenafil
-
preincubation with cGMP increases catalytic activity for cGMP degradation, but also for binding of inhibitor
vardenafil
Q8CG03
potent PDE5 inhibitor
vardenafil
-
selective inhibitor of phosphodiesterase-5
vardenafil
-
vardenafil inhibits the activity of PDE-5 and results in relaxation of smooth muscle
vardenafil
-
-
vardenafil
-
-
zaprinast
-
-
zaprinast
-
0.0006 mM, 50% inhibition
zaprinast
O76083
0.046 mM, 50% inhibition of PDE9A5, 0.043 mM, 50% inhibition of PDE9A1
zaprinast
-
0.00046 mM, 50% inhibition in sham-operated rats
zaprinast
-
0.0002 mM, 50% inhibition
zaprinast
-
0.0003 mM, 50% inhibition
zaprinast
-
0.000053 mM, 50% inhibition
zaprinast
-
IC50: 0.00065 mM
zaprinast
Q2V2M6
IC50: 0.0038 mM for wild-type enzyme and 0.0056 for mutant enzyme G788A
zaprinast
-
-
zaprinast
-
IC50: 0.24 mM
zaprinast
Q864F1
;
zaprinast
-
-
Zn2+
-
complete inhibition above 0.1 mM
Zn2+
-
strong inhibition above 0.01 mM, almost complete inhibition at 0.1 mM
Zn2+
-
strong inhibition above 0.01 mM, complete inhibition at 0.1 mM
Milrinone
-
IC50: 0.0491 mM, PDE5
additional information
Q2V2M6
3-isobutyl-1-methylxanthine, theophylline and the antimalarial chloroquine show IC50-value of over 0.1 mM
-
additional information
-
recombinant and native PDE6s exhibit differential sensitivity to inhibitors. This data caution the use of recombinant catalytic subunits of PDE6 in drug discovery or in structural/functional studies
-
additional information
-
red wine and extract from grape skin inhibit isoenzyme PDE5A1 activity, seed extract has negligible effect. Polyphenol-induced vasorelexation may be sustained by smooth muscle PDE inhibition by anthocyanins present in red wines and grapes. trans-Resveratrol and trans-piceid exhibit negligible effects. hydroxycinnamates are completely inactive
-
additional information
-
Gingko biloba dimeric flavonoids inhibit the cGMP-specific PDE5A1
-
additional information
-
not inhibited by quercetin, quercetin-3,7,3',4'-O-tetramethylether, quercetin-3,5,7,3',4'-O-pentaacetate, and quercetin-3,7,4'-O-trimethylether
-
additional information
-
not affected by cilostazol and rolipram
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8-Bromo-cGMP
-
-
alpha-subunit of transducin
-
activation of isoform PDE6 by binding to the inhibitory gamma-subunit
-
alpha-subunit of transducin
-
in presence of transducin alpha-subunit-GTP, the inhibitory gamma subunit of PDE6 remains attached to the rest of the PDE6 molecule, but after conversion to transducin alpha-subunit-GDP, the PDE6 gamma subunit may dissociate from PDE6 and exchange with a cytoplasmic pool
-
cGMP
-
allosteric activation
cGMP
O76074
activation by suggested binding to PDE5 GAF domain
cGMP
-
allosteric activation, cGMP binds to F205 in N-terminal GAF-domain of PDE5
cGMP
-
maximal 2.4fold activation below 0.001 mM, half-maximal activation at 0.00016 mM, inhibition above 0.001 mM
cGMP
-
allosteric activation
cGMP
-
preincubation with cGMP increases catalytic activity for cGMP degradation, this increase may be caused by binding of cGMP to either the PDE5 allosteric sites, catalytic sites, or both. Full-length GAF-B subdomain conjoined with catalytic domain is sufficient for this conversion
cGMP
-
cGMP binding to the GAF-A domain is necessary to achieve full activation of PDE5, 3fold activation of blood platelet PDE5 occurs at 0.02 mM cGMP
cyclic AMP-dependent protein-kinase
-
phosphorylates alpha- and beta-subunit
-
Glycylglycine buffer
-
-
GTP
-
activation
GTP
-
dependent
Imidazole buffer
-
-
-
light
-
activation
-
light
-
activation; activation by photolyzed rhodopsin
-
light
-
activation
-
light
-
activation by a rod G-protein
-
light
-
activation by photolyzed rhodopsin
-
PgammaPDE6
Q8UUY2, Q8UUY6, Q8UUY7
regulatory subunit of PDE6, activation of cGMP binding to GAF domains of PDE6alpha or beta subunit
-
Protein kinase C
-
phosphorylates alpha- and gamma-subunit
-
S-modulin
-
-
-
S-nitrosoglutathione
-
stimulation of isoform PDE5 phosphorylation and activity, resulting in increased levels of cGMP in gastric smooth muscle cells. Concurrent activation of cells with acetylcholine augments stimulation and attenuates cGMP levels
stable toxin
O76074
possibly due to an increase in cGMP resulting from stable toxin treatment
-
Transducin
-
activation
-
Transducin
-
heterotrimeric G protein
-
Triton X-100
-
-
Trypsin
-
-
-
light
-
light stimulates PDE6 activation, rapid reduction in cGMP, closure of Na+/Ca2+ channels and reduced Ca2+ influx
-
additional information
-
not activated by 8-bromo-cGMP
-
additional information
-
protein kinase G-mediated phosphorylation up-regulates activity, PP1 phosphatase-mediated dephosphorylation down-regulates activity
-
additional information
-
phosphorylation acts in concert with allosteric cGMP binding to stimulate the PDE5 catalytic site, which should promote negative feedback regulation of the cGMP pathway in intact cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.012
2'-O-anthraniloyl cGMP
-
37C, pH 7.4
0.0247
2'-O-anthraniloyl-cGMP
-
phosphorylated PDE5, at 30C with 50 mM Tris-HCl, pH 7.5
0.0651
2'-O-anthraniloyl-cGMP
-
unphosphorylated PDE5, at 30C with 50 mM Tris-HCl, pH 7.5
0.00098
3',5'-cAMP
-
30C, pH 8.0, PDE5
0.0281
3',5'-cAMP
-
wild type enzyme, in 50 mM KCl, 10 mM EGTA, 1.92 mM MgCl2, 1 mM dithiothreitol, and 50 mM HEPES, pH 7.4
0.0354
3',5'-cAMP
-
mutant enzyme C1128S, in 50 mM KCl, 10 mM EGTA, 1.92 mM MgCl2, 1 mM dithiothreitol, and 50 mM HEPES, pH 7.4
0.717
3',5'-cAMP
-
enzyme from cone
0.82
3',5'-cAMP
-
enzyme from rod
0.00032
3',5'-cGMP
-
low affinity components
0.00065
3',5'-cGMP
Q2V2M6
wild-type enzyme
0.00077
3',5'-cGMP
Q2V2M6
mutant enzyme G788A
0.002
3',5'-cGMP
-
-
0.003
3',5'-cGMP
-
-
0.0036
3',5'-cGMP
-
chimaeric PDE5/PDE6 catalytic domain, pH and temperature not specified in the publication
0.0047
3',5'-cGMP
-
-
0.0056
3',5'-cGMP
-
-
0.0319
3',5'-cGMP
-
high affinity components
0.037
3',5'-cGMP
-
-
0.065
3',5'-cGMP
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
0.066
3',5'-cGMP
-
-
0.078
3',5'-cGMP
-
trypsin activated enzyme
0.092 - 0.973
3',5'-cGMP
-
-
0.13
3',5'-cGMP
-
value of the dark
1
3',5'-cGMP
-
8fold higher on illumination
0.00022
cGMP
-
-
0.00025
cGMP
O76083
splice variant PDE9A1
0.00039
cGMP
O76083
splice variant PDE9A5
0.0008
cGMP
-
30C, pH 7.4
0.001
cGMP
-
30C, pH 7.4, platelet PDE5
0.0015
cGMP
-
37C, pH 7.4
0.002
cGMP
-
30, pH 7.4
0.0023
cGMP
-
30C, pH 7.4
0.0029
cGMP
O76074
wild-type, pH 7.5, 30C
0.005
cGMP
-
isoform PDE5, high affinity form, pH 7.0, 22C
0.0052
cGMP
-
-
0.0058
cGMP
-
37C, pH 7.4, recombinant isoenzyme PDE5A2
0.006
cGMP
-
37C, pH 7.4, recombinant isoenzyme PDE5A3
0.0061
cGMP
O76074
mutant Y612F, pH 7.5, 30C
0.0062
cGMP
-
37C, pH 7.4, recombinant isoenzyme PDE5A1
0.0071
cGMP
O76074
mutant H613A, pH 7.5, 30C
0.0159
cGMP
O76074
mutant V782A, pH 7.5, 30C
0.02
cGMP
-
isoform PDE5, low affinity form, pH 7.0, 22C
0.0277
cGMP
O76074
mutant L765A, pH 7.5, 30C
0.0297
cGMP
O76074
mutant F786A, pH 7.5, 30C
0.0416
cGMP
O76074
mutant Y612A, pH 7.5, 30C
0.172
cGMP
O76074
mutant F820A, pH 7.5, 30C
0.182
cGMP
O76074
mutant Q817A, pH 7.5, 30C
0.8
cGMP
-
isoform PDE6, high affinity form, pH 7.0, 22C
1.6
cGMP
-
isoform PDE6, low affinity form, pH 7.0, 22C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.55
3',5'-cGMP
-
chimaeric PDE5/PDE6 catalytic domain, pH and temperature not specified in the publication
4400
3',5'-cGMP
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
0.00083
cGMP
O76074
mutant H613A, pH 7.5, 30C
0.04
cGMP
O76074
mutant F820A, pH 7.5, 30C
0.8
cGMP
O76074
mutant Y612A, pH 7.5, 30C
1.3
cGMP
O76074
mutant L765A, pH 7.5, 30C
1.7
cGMP
O76074
mutant Y612F, pH 7.5, 30C
2.2
cGMP
O76074
wild-type, pH 7.5, 30C
2.5
cGMP
O76074
mutant V782A, pH 7.5, 30C
3.7
cGMP
O76074
mutant F786A, pH 7.5, 30C
3.8
cGMP
O76074
mutant Q817A, pH 7.5, 30C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000045
1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazol[3,4d]-pyrimidin-4-(5H)-one
-
sham-operated rats
0.000045
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
-
0.000176
2-bromo-5-ethyl-7,8-dihydro-1-[(4-hydroxyphenyl)methyl]-7(R)-(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
30C, pH 7.4, native PDE6
0.0003616
2-bromo-5-ethyl-7,8-dihydro-1-[(4-hydroxyphenyl)methyl]-7(R)-(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.0006608
2-bromo-5-ethyl-7,8-dihydro-1-[(4-hydroxyphenyl)methyl]-7(R)-(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
30C, pH 7.4, recombinant cone PDE6alpha'
1
3',5'-cAMP
-
-
0.0000487
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.0000546
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
-
30C, pH 7.4, recombinant cone PDE6alpha'
0.0007215
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
-
30C, pH 7.4, native PDE6
0.0085
3-isobutyl-1-methylxanthine
-
chimaeric PDE5/6 catalytic domain, pH and temperature not specified in the publication
0.01212
3-isobutyl-1-methylxanthine
-
30C, pH 7.4, native PDE6
0.06084
3-isobutyl-1-methylxanthine
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.09485
3-isobutyl-1-methylxanthine
-
30C, pH 7.4, recombinant
0.0012
5-(2-propoxyphenyl)-2,3-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
0.0000173
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
30C, pH 7.4, native PDE6
0.001206
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.001605
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
30C, pH 7.4, recombinant cone PDE6alpha'
0.0000026
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.0000036
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
-
30C, pH 7.4, recombinant cone PDE6alpha'
0.0000183
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
-
30C, pH 7.4, native PDE6
1.8
cAMP
-
-
0.078
cone Pgamma subunit
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
-
0.14
cone Pgamma subunit
-
recombinant human cone PDE6AB, pH and temperature not specified in the publication
-
0.0000035
E4021
-
30C, pH 7.4, native PDE6
0.0001014
E4021
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.0001735
E4021
-
30C, pH 7.4, recombinant cone PDE6alpha'
0.0015
Pgamma-inhibitory peptide
-
chimaeric PDE5/6 catalytic domain, pH and temperature not specified in the publication
-
0.0029
Pgamma-inhibitory peptide Pgamma63-87
-
chimaeric PDE5/6 catalytic domain, pH and temperature not specified in the publication
-
0.0121
Pgamma-inhibitory peptide Pgamma70-87
-
chimaeric PDE5/6 catalytic domain, pH and temperature not specified in the publication
-
0.105
rod Pgamma subunit
-
recombinant human cone PDE6AB, pH and temperature not specified in the publication
-
0.155
rod Pgamma subunit
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
-
0.000013
sildenafil
-
37C, pH 7.4, recombinant isoenzyme PDE5A3
0.000014
sildenafil
-
37C, pH 7.4, recombinant isoenzyme PDE5A2
0.0000245
sildenafil
-
30C, pH 7.4, native PDE6
0.000025
sildenafil
-
chimaeric PDE5/6 catalytic domain, pH and temperature not specified in the publication
0.000028
sildenafil
-
37C, pH 7.4, recombinant isoenzyme PDE5A1
0.0000936
sildenafil
-
30C, pH 7.4, recombinant rod PDE6alphabeta
0.0000984
sildenafil
-
30C, pH 7.4, recombinant cone PDE6alpha'
0.0001778
zaprinast
-
30C, pH 7.4, native PDE6
0.00031
zaprinast
-
sham-operated rats
0.0013
zaprinast
-
37C, pH 7.4, recombinant isoenzyme PDE5A2
0.0016
zaprinast
-
37C, pH 7.4, recombinant isoenzyme PDE5A3
0.0032
zaprinast
-
37C, pH 7.4, recombinant isoenzyme PDE5A1
0.01145
zaprinast
-
30C, pH 7.4 cone PDE6alpha'
0.01438
zaprinast
-
30C, pH 7.4 rod PDE6alphabeta
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0121
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0121 mM, PDE5
0.00067
(2Z)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
-
IC50: 0.00067 mM, PDE5
0.053
(E)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone O-carbamoyl oxime
-
-
0.019
1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
-
-
0.000055
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
i.e. BAY 73-6691, IC50: 55 nM
0.0001
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
i.e. BAY 73-6691, IC50: 100 nM
0.0000004
1-(2-ethoxyethyl)-3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00001
1-(3-chloro-4-methoxybenzyl)-3-(cis-4-hydroxycyclohexyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-carbonitrile
-
-
0.0000037
1-[4-[(1,3-benzodioxol-5-ylmethyl)amino]-6-chloroquinazolin-2-yl]piperidine-4-carboxylic acid
-
-
0.00069
2,2',2'',2'''-[(4,8-dipiperidin-1-ylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
-
-
0.000005
2-(2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
-
-
0.23
2-(2-methylpyridin-4-yl)methyl-4-(3,4,5-trimethoxyphenyl)-8-(pyrimidin-2-yl)methoxy-1,2-dihydro-1-oxo-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride
-
i.e. T-0156, IC50: 0.23 mM, potent and highly selective phosphodiesterase type 5 inhibitor
0.00001
2-(2-propoxyphenyl)-1,7-dihydro-6H-purin-6-one
-
-
0.0000017
2-(5-amino-2-propoxyphenyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
0.0000065
2-(5-[[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl]-2-propoxyphenyl)-5-methylquinazolin-4(3H)-one
-
-
0.0027
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0027 mM, PDE5
0.00001
2-methoxy-7-methyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazin-6(5H)-one
-
-
0.0000007
2-[2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl]-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
-
-
0.00000022
3-(4-ethylpiperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.0035
3-(cyclopentylmethoxy)-N-(2,6-dichlorophenyl)-4-methoxybenzamide
-
-
0.017
3-(cyclopropylmethoxy)-N-(2,6-dichlorophenyl)-4-(difluoromethoxy)benzamide
-
-
0.00000112
3-([2-[(2-hydroxyethyl)amino]ethyl]amino)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000648
3-ethyl-5-(4-methyl-1,4-diazepan-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000392
3-ethyl-5-(morpholin-4-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.0000003
3-ethyl-5-(piperazin-1-yl)-1-(2-propoxyethyl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000086
3-ethyl-5-(piperazin-1-yl)-1-[2-(propan-2-yloxy)ethyl]-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000065
3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000015
3-ethyl-5-(piperazin-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000007
3-ethyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000009
3-ethyl-N-(4-fluorophenyl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000328
3-ethyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000101
3-ethyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000035
3-ethyl-N5-(1-methylpiperidin-4-yl)-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
-
pH and temperature not specified in the publication
0.0000019
3-isobutyl-1-methylxanthine
O76074
mutant Y612F, pH 7.5, 30C
0.000003
3-isobutyl-1-methylxanthine
O76074
mutant L765A, pH 7.5, 30C
0.0000035
3-isobutyl-1-methylxanthine
O76074
wild-type, pH 7.5, 30C
0.0000423
3-isobutyl-1-methylxanthine
O76074
mutant H613A, pH 7.5, 30C
0.0000425
3-isobutyl-1-methylxanthine
O76074
mutant V782A, pH 7.5, 30C
0.0000433
3-isobutyl-1-methylxanthine
O76074
mutant F786A, pH 7.5, 30C
0.000152
3-isobutyl-1-methylxanthine
O76074
mutant Y612A, pH 7.5, 30C
0.000214
3-isobutyl-1-methylxanthine
O76074
mutant Q817A, pH 7.5, 30C
0.000327
3-isobutyl-1-methylxanthine
O76074
mutant F820A, pH 7.5, 30C
0.032
3-isobutyl-1-methylxanthine
-
IC50: 0.032 mM
0.00000014
3-methyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000094
3-methyl-5-[(3S)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000184
3-methyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000078
3-methyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000238
3-[(1R,4R)-2,5-diazabicyclo[2.2.1]hept-2-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000025
3-[(2-aminoethyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000021
3-[4-(2,2-dihydroxypropyl)-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000072
3-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.0000002
3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]-pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.0000002
3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000108
3-[4-(3-hydroxypropyl)-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000018
3-[4-(3-hydroxypropyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000023
3-[4-[(2R)-2-hydroxypropyl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.0000003
3-[4-[(2R,3R)-3-hydroxybutan-2-yl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000031
3-[4-[(2S)-2-hydroxypropyl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000033
3-[4-[(2S,3R)-3-hydroxybutan-2-yl]-1,4-diazepan-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.000014
4-(1,3-benzodioxol-5-ylmethoxy)-2-(1H-imidazol-1-yl)-5-phenylpyrimidine
-
-
0.053
4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylic acid
-
-
0.00000296
4-[3-ethyl-7-(pyrimidin-4-ylamino)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazin-2-one
-
pH and temperature not specified in the publication
0.00000315
5-(1,4-diazepan-1-yl)-3-ethyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.00000979
5-(1,4-diazepan-1-yl)-3-methyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
pH and temperature not specified in the publication
0.081
5-(2-propoxyphenyl)-3,6-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
0.0025
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0025 mM, PDE5
0.00000328
7-(6-methoxypyridin-3-yl)-3-(piperazin-1-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one
-
pH and temperature not specified in the publication
0.00000034
8-(5-[[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]sulfonyl]-2-propoxyphenyl)-6-propyl-6,6a,9,9a-tetrahydro-5H-[1,2,4]triazolo[3,4-i]purin-5-one
-
-
0.0055
8-methoxymethyl-isobutylmethylxanthine
-
isoform PDE5, pH and temperature not specified in the publication
0.0117
amentoflavone
-
IC50: 0.0117 mM
0.2296
amrinone
-
IC50: 0.2296 mM, PDE5
0.0000011
benzamidenafil
-
PDE-5, pH and temperature not specified in the publication
0.00002
benzamidenafil
-
PDE-6, pH and temperature not specified in the publication
0.00152
bilobetin
-
IC50: 0.00152 mM
0.0000405
Cilostamide
-
bladder homogenate, 30C, pH 7.0
0.006
Cilostamide
-
IC50: 0.006 mM, PDE5
0.0152
Cilostamide
-
IC50: 0.0152 mM, PDE5
0.0044
cilostazol
-
IC50: 0.0044 mM, PDE5
0.023
dioclein
-
isoform PDE5, pH and temperature not specified in the publication
0.015
diosmetin
-
IC50: 0.015 mM, PDB5
0.0000109
dipyridamole
-
bladder homogenate, 30C, pH 7.0
0.00026
dipyridamole
-
IC50: 0.00026 mM, PDE5
0.022
dipyridamole
Q2V2M6
IC50: 0.022 mM
0.023
dipyridamole
-
IC50: 0.023 mM
0.046
E4021
Q2V2M6
IC50: 0.046 mM
0.073
genistein
-
IC50: 0.073 mM, PDB5
0.00059
ginkgetin
-
IC50: 0.00059 mM
0.0193
luteolin
-
IC50: 0.0193 mM, PDB5
0.0354
malvidin
-
IC50: 0.0354 mM
0.0116
malvidin-3-O-beta-glucoside
-
IC50: 0.0116 mM
0.0491
Milrinone
-
IC50: 0.0491 mM, PDE5
0.0000026
N-(3-chloro-4-methoxybenzyl)-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine
-
-
0.000003
N-[3-(1,3-dimethyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-propoxyphenyl]methanesulfonamide
-
-
0.0000035
N-[3-(4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]piperidine-1-carboxamide
-
-
0.000018
N-[3-(4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]morpholine-4-carboxamide
-
-
0.00000952
N5-(2-aminoethyl)-3-ethyl-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
-
pH and temperature not specified in the publication
0.0137
quercetin-3,5,7,3',4'-O-pentamethylether
-
PDE5
0.0111
quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate
-
PDE5
0.0869
quercetin-3-O-methylether
-
PDE5
0.000021
quinazolinamine
-
IC50: 0.000021 mM, PDE5
0.0089
RP-73401
-
IC50: 0.0089 mM, PDE5
0.00324
sciadopitysin
-
IC50: 0.00324 mM
0.0199
sequoiaflavone
-
IC50: 0.0199 mM
0.0000013
sildenafil
O76074
mutant Y612F, pH 7.5, 30C
0.0000016
sildenafil
-
non-activated PDE5 from blood platelets, at 0.0001 mM cGMP, at pH 7.5 and 30C
0.000002
sildenafil
-
isoform PDE5, pH and temperature not specified in the publication
0.0000032
sildenafil
-
bladder homogenate, 30C, pH 7.0
0.0000033
sildenafil
O76074
wild-type, pH 7.5, 30C
0.0000036
sildenafil
-
IC50: 3.6 nM
0.0000037
sildenafil
-
IC50: 3.7 nM, 1000fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.0000037
sildenafil
-
IC50: 3.7 nM
0.0000043
sildenafil
-
PDE-5, pH and temperature not specified in the publication
0.000005
sildenafil
-
cGMP-activated PDE5 from blood platelets, at 0.0001 mM cGMP, at pH 7.5 and 30C
0.0000078
sildenafil
-
IC50: 7.8 nM
0.0000085
sildenafil
-
IC50: 8.5 nM, PDE5
0.0000101
sildenafil
O76074
mutant L765A, pH 7.5, 30C
0.0000132
sildenafil
O76074
mutant H613A, pH 7.5, 30C
0.000015
sildenafil
-
PDE-6, pH and temperature not specified in the publication
0.0000206
sildenafil
O76074
mutant F786A, pH 7.5, 30C
0.000025
sildenafil
-
IC50: 0.000025 mM
0.0000319
sildenafil
O76074
mutant V782A, pH 7.5, 30C
0.000049
sildenafil
-
IC50: 49 nM, PDE6
0.0000983
sildenafil
O76074
mutant Y612A, pH 7.5, 30C
0.000141
sildenafil
O76074
mutant Q817A, pH 7.5, 30C
0.000235
sildenafil
O76074
mutant F820A, pH 7.5, 30C
0.005
sildenafil
-
IC50: 0.005 mM
0.01
sildenafil
-
IC50: above 10000 nM, PDE9
0.056
sildenafil
Q2V2M6
IC50: 0.056 mM
0.041
T-1032
-
IC50: 0.041 mM
0.0000018
tadalafil
-
IC50: 1.8 nM, 40fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.0000018
tadalafil
-
IC50: 1.8 nM
0.0000022
tadalafil
O76074
wild-type, pH 7.5, 30C
0.0000058
tadalafil
O76074
mutant Y612F, pH 7.5, 30C
0.00000607
tadalafil
-
bladder homogenate, 30C, pH 7.0
0.0000067
tadalafil
O76074
mutant V782A, pH 7.5, 30C
0.0000091
tadalafil
O76074
mutant L765A, pH 7.5, 30C
0.0000094
tadalafil
-
IC50: 9.4 nM, PDE5
0.0000375
tadalafil
O76074
mutant F786A, pH 7.5, 30C
0.000081
tadalafil
O76074
mutant H613A, pH 7.5, 30C
0.000112
tadalafil
O76074
mutant Y612A, pH 7.5, 30C
0.00021
tadalafil
O76074
mutant Q817A, pH 7.5, 30C
0.000301
tadalafil
O76074
mutant F820A, pH 7.5, 30C
0.01
tadalafil
-
IC50: above 10000 nM, PDE9
0.0000004
trans-4-([2-[(3-chloro-4-methoxyphenyl)carbamoyl]-4-cyanophenyl]carbamoyl)cyclohexanecarboxylic acid
-
-
0.00000006
vardenafil
O76074
mutant Y612F, pH 7.5, 30C
0.000000091
vardenafil
-
IC50: 0.091 nM
0.00000012
vardenafil
O76074
wild-type, pH 7.5, 30C
0.0000003
vardenafil
-
bladder homogenate, 30C, pH 7.0
0.00000049
vardenafil
O76074
mutant L765A, pH 7.5, 30C
0.00000078
vardenafil
O76074
mutant H613A, pH 7.5, 30C
0.00000083
vardenafil
O76074
mutant F786A, pH 7.5, 30C
0.00000089
vardenafil
-
IC50: 0.89 nM, PDE5
0.000011
vardenafil
-
IC50: 11 nM, PDE6
0.0000147
vardenafil
O76074
mutant Y612A, pH 7.5, 30C
0.0000275
vardenafil
O76074
mutant V782A, pH 7.5, 30C
0.0000537
vardenafil
O76074
mutant F820A, pH 7.5, 30C
0.0000613
vardenafil
O76074
mutant Q817A, pH 7.5, 30C
0.000091
vardenafil
-
IC50: 0.091 nM, 9300fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.00337
vardenafil
-
IC50: 3370 nM, PDE9
0.0000088
zaprinast
-
bladder homogenate, 30C, pH 7.0
0.00013
zaprinast
-
pH and temperature not specified in the publication
0.00065
zaprinast
-
IC50: 0.00065 mM
0.0023
zaprinast
-
PDE5
0.0038
zaprinast
Q2V2M6
IC50: 0.0038 mM for wild-type enzyme and 0.0056 for mutant enzyme G788A
0.24
zaprinast
-
IC50: 0.24 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000012
-
-
0.00061
-
partially purified PDE5 from N18TG2 neuroblastoma cells
1.44
-
partially purified PDE5 from NG108-15 neuroblastoma cells
20 - 100
-
unactivated purified enzyme
1200 - 1500
-
trypsin-activated enzyme
additional information
-
-
additional information
-
assay method
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.3
-
with Tris-acetate as buffer
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.5
-
almost no activity at pH 6.0 and 8.5, respectively
6.5 - 8.5
-
almost no activity at pH 6.5 and pH 8.5, respectively
6.5 - 8.5
-
very low activity at pH 6.5 and 8.5, respectively
7 - 8
-
3fold increase in activity from pH 7 to pH 8
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
higher expression than in corpus cavernosum
Manually annotated by BRENDA team
-
PDE5, PDE6, PDE9
Manually annotated by BRENDA team
-
in the vasculature, PDE5 is the predominant PDE isoform involved in degrading cGMP
Manually annotated by BRENDA team
-
PDE5 vascular expression is decreased in arteries from angiotensin II hypertensive rats compared to control rats
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
PDE5 vascular expression is decreased in arteries from angiotensin II hypertensive rats compared to control rats
-
Manually annotated by BRENDA team
-
vascular endothelium and muscle fibers
Manually annotated by BRENDA team
-
vascular endothelium and muscle fibers, castration decreases and T supplementation restores PDE5 gene expression
Manually annotated by BRENDA team
-
vascular endothelium and muscle fibers only
Manually annotated by BRENDA team
-
high activity in intact platetelts
Manually annotated by BRENDA team
-
high expression of PDE5 in blood platelets
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
-
parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum
Manually annotated by BRENDA team
-
isoform PDE5A shows an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoform PDE9A does not change with age. Age-related increases in PDE11A4, and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents, as are age-related increases in PDE8A3 protein expression in the striatum
Manually annotated by BRENDA team
-
phosphodiesterase 5 is exclusively detected in smooth muscle cells of the wall, no activity in vascular endothelial layer
Manually annotated by BRENDA team
Q8QZV1
strongest PDE9A expression in Purkinje cells
Manually annotated by BRENDA team
-
strongest PDE9A expression in Purkinje cells
Manually annotated by BRENDA team
-
PDE5 is limited to the smooth muscle of the clitoral erectile tissue, presence of isoform PDE5 in smooth muscle of the clitoral erectile tissue
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
PDE5A1 and PDE5A3 show an increase from embryonic day 10 to embryonicday18 and from embryonic day 18 to 5-day post-hatching chick. PDE5A2 undergoes a marked increase (about 38fold) in the first period and remains nearly constant between embryonic day 18 and 5-day post-hatching chicken
Manually annotated by BRENDA team
-
rod outer segment
Manually annotated by BRENDA team
-
whole myocardium from failing hearts have 50% lower PDE5A expression and 30% less total and EMD82639-inhibitable cGMP-PDE activity
Manually annotated by BRENDA team
-
enzyme isoform PDE5 mRNA and protein are markedly upregulated in hypertrophied human right ventricle
Manually annotated by BRENDA team
-
enzyme isoform PDE5 mRNA and protein are markedly upregulated in hypertrophied right ventricle
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
Q8QZV1
pyramidal cells and granule cells
Manually annotated by BRENDA team
-
pyramidal cells and granule cells
Manually annotated by BRENDA team
-
colon cancer cell
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
-
28fold decrease in cGMP-phosphodiesterase after treatment of animals with 50 mg/kg cyclosporin A
Manually annotated by BRENDA team
-
inner medullary collecting duct cells
Manually annotated by BRENDA team
-
increased intrarenal isoform PDE5 level mediates the blunted natriuretic response to atrial natriuretic peptide during pregnancy and may contribute to the physiological volume expansion
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
phosphodiesterase 5
Manually annotated by BRENDA team
O76083
very low expression level
Manually annotated by BRENDA team
-
very low expression
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
highest PDE5 expression
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
muscle fibers of bladder
Manually annotated by BRENDA team
-
phosphodiesterase 5
Manually annotated by BRENDA team
-
pregnant and non-pregnant
Manually annotated by BRENDA team
-
myometrial cell, level of isoform PDE5 decreases in all conditions that inhibit proliferation
Manually annotated by BRENDA team
-
PDE5 is induced in neuroblastoma-glioma NG108-15 cells after dibutyryl treatment
Manually annotated by BRENDA team
-
PFE9A gene expression is higher in neutrophils from sickle cell disease individuals compared to control cells
Manually annotated by BRENDA team
-
PDE5 plays a role in regulating spontaneous maturation of oocytes
Manually annotated by BRENDA team
-
PDE5 is present in cumulus cells of big, antral follicles
Manually annotated by BRENDA team
-
in freshly isolated peritoneal exudate macrophage, isoform PDE5 is expressed. After 24h of cultures, PDE5 is no longer present
Manually annotated by BRENDA team
-
phosphodiesterase 5
Manually annotated by BRENDA team
Q8UUY2, Q8UUY6, Q8UUY7
rod outer segment
Manually annotated by BRENDA team
-
outer segments of rod and cone photoreceptors
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
main distribution in glandular and subglandular areas
Manually annotated by BRENDA team
-
PDE5 is expressed in all Purkinje cells
Manually annotated by BRENDA team
-
PFE9A gene expression is higher in reticulocytes from sickle cell disease individuals compared to control cells
Manually annotated by BRENDA team
-
two distinct isoenzymes exist in rods (PDE6R) and cones (PDE6C)
Manually annotated by BRENDA team
Bos taurus PDE6
-
PDE6
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
PDE6alpha' is expressed exclusively in cone photoreceptors, its activity is important for the survival of cone photoreceptors
Manually annotated by BRENDA team
-
outer segment membrane
Manually annotated by BRENDA team
-
rod photoreceptor
Manually annotated by BRENDA team
-
in the rod photoreceptor PDE is entirely localized within the rod outer segment
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
smooth muscle specific expression of PDE5A3
Manually annotated by BRENDA team
-
presence of isoform PDE5 in smooth muscle of the clitoral erectile tissue
Manually annotated by BRENDA team
-
splice variant PDE5A3 is specific to smooth muscle
Manually annotated by BRENDA team
-
of central cavernous arteries, phosphodiesterase 5
Manually annotated by BRENDA team
-
PDE5 protein levels are strongly regulated by the mitotic activity of the smooth muscle cells, they are increased in quiescent, contractile myometrial cultures, and conditions in which proliferation is inhibited, isoform PDE5 protein level is strongly regulated by the mitotic activity of cells
Manually annotated by BRENDA team
O54735
cervical spinal cord, expression of isoforms PDE2, PDE5, and PDE9 in all lamina, in ventral motor neurons and in ependymal cells lining the central canal. Study on the influence of enzyme activity on NO-stimulated cGMP levels
Manually annotated by BRENDA team
O76083
highest expression levels of splice variants PDE9A5 and PDE9A1, expression levels of PDE9A1 in descending order, spleen, prostate, colon, kidney, brain, small intestine, heart, liver and lung, expression levels of PDE9A5 in descending order, spleen, brain, prostate, colon, small intestine, kidney, lung, heart and liver
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
PDE5 is present in young and adult gland
Manually annotated by BRENDA team
O76074
colonic T84 cells
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
vascular smooth muscle cells, Leydig cells and peritubular cells, phosphodiesterase 5
Manually annotated by BRENDA team
-
wide distribution of enzyme isoform PDE5, nerve-induced relaxation of urethral preparations are enhanced at low concentrations of enzyme inhibitors sildenafil, vardenafil, and tadalafil, with direct smooth muscle-relaxant actions of the inhibitors at high concentrations
Manually annotated by BRENDA team
-
constitutively present. No change in PDE-5 protein expression throughout pregnancy
Manually annotated by BRENDA team
-
detected in all different muscular layers, as well as endothelial and smooth muscle cells of the blood vessels. No activity in luminal epithelial cells
Manually annotated by BRENDA team
-
detected in all different muscular layers, as well as endothelial and smoothmuscle cells of the blood vessels. No activity in luminal epithelial cells
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
additional information
-
isoform PDE5 is present in all tissues examined, with heart and cardiomycete being contentious. Splice variants PDE5A1 and PDE5A2 are ubiquitous
Manually annotated by BRENDA team
additional information
-
not detected in lymph node, mammary gland, ovary, skeletal muscle, testicle, and uterus
Manually annotated by BRENDA team
additional information
-
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
PDE5 is localized in discrete cytoplasmic foci, isoform PDE5 is localized in discrete cytoplasmic foci
Manually annotated by BRENDA team
-
subcelluar distribution
Manually annotated by BRENDA team
O76083
splice variant PDE9A5
Manually annotated by BRENDA team
-
C1128S-PDE5/6 mutant form is located primarily in the cytosol, although some residual association occurs at the apical membrane
Manually annotated by BRENDA team
-
rod outer segment membrane
Manually annotated by BRENDA team
-
generation of transgenic animals with targeted expression of DmPDE6 to tubule type I (principal) cells. This reveals localization of DmPDE6 primarily at the apical membranes
Manually annotated by BRENDA team
-
of rod outer segment
Manually annotated by BRENDA team
-
approximately 37% of cGMP degradation activity is localized in the detergent-resistant membrane
Manually annotated by BRENDA team
O76083
splice variant PDE9A1
Manually annotated by BRENDA team
Q8UUY2, Q8UUY6, Q8UUY7
peripherally attached under dark conditions
Manually annotated by BRENDA team
-
PDE5/6 is exclusively associated with the apical membrane
Manually annotated by BRENDA team
-
approximately 45% of cGMP degradation activity is localized in the detergent-soluble fractions
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60000
Q864F1
PDE6C immunodetection shows two bands at about 60000 and 85000 Da, SDS-PAGE
692087
72000
-
PDE9, SDS-PAGE
691533
85000
Q864F1
PDE6C immunodetection shows two bands at about 60000 and 85000 Da, SDS-PAGE
692087
90000 - 99000
-
the antibody against PDE5 recognizes a 90000/99000 Da doublet band, SDS-PAGE
711772
98000
O54735
theoretical value
711744
100000
Q864F1
about 100000 Da, PDE5A, SDS-PAGE
692087
125000
-
recombinant enhanced green fluorescent protein fusion protein of human cone PDE6C
712394
130000
-
SDS-PAGE
690833
178000
-
calculated native molecular weight
135355
182000
-
gel filtration; gel filtration, sucrose density gradient centrifugation
135278
200000
O76074
gel filtration
650813
260000
-
gel filtration
135337
400000
-
gel filtration
135340
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
88000, alpha-subunit, + 84000, beta-subunit, + 1100, gamma-subunit, inhibitory, SDS-PAGE
?
-
88000, alpha-subunit + 84000, beta-subunit + 13000-14000, gamma-subunit, SDS-PAGE
?
-
PDE holoenzyme consists of a catalytic dimer Palpa,beta to which the inhibitory Pgamma subunits bind
?
Q8QZV1
x * 61756, deduced from nucleotide sequence
?
-
x * 98000, immunoblot
?
-
x * 10000, SDS-PAGE, isoform PDE6 gamma-subunit
?
O76074
x * 99000, SDS-PAGE of recombinant His-tagged protein
dimer
-
2 * 92000, sucrose density gradient centrifugation
dimer
-
2 + 93000, SDS-PAGE
dimer
O76074
2 * 105000, immunoblot
dimer
-
full-length PDE6C, X-ray crystallography
tetramer
-
-
tetramer
-
an alpha- and beta-subunit, catalytic and two identical gamma subunits, noncatalytic, no method mentioned
tetramer
Q8UUY2, Q8UUY6, Q8UUY7
alpha,beta,gamma2, PDE6 consists of two homologous catalytic subunits and two identical regulatory subunits
tetramer
Q8UUY2, Q8UUY6, Q8UUY7
alpha,beta,gamma2, PDE6 consits of two homologous catalytic subunits and two identical regulatory subunits
tetramer
-
alphabeta(gamma)2
tetramer
-
alphabeta(gamma)2,PDE6 consistis of catalytic alpha and beta subunits and two inhibitory gamma subunits
monomer
-
PDE6C GAF A domain is monomeric and does not contain sufficient structural determinants to form a homodimer as found in full-length PDE6C, X-ray crystallography
additional information
-
two homologous noncatalytic cyclic GMP-binding sites located in the N-terminal half of PDE5
additional information
-
alpha-subunit of transducin interacts with the inhibitory gamma subunit of PDE6 thereby activating the enzyme. Interaction requires activated alpha-subunit of transducin and involves the C-terminus of PDE6 gamma-subunit, particularly residue 73
additional information
-
binding sites of catalytic subunits alpha and beta of PDE6 are accessible to excess inhibitory subunit gamma in the light, once endogenous gamma subunit has been displaced from its binding site by transducin alpha-subunit-GTP
additional information
-
enzyme forms a catalytic Palphabeta heterodimer in complex with two Pgamma inhibitory subunits. The N-terminal V16-F30 region of inhibitory subunit Pgamma interacts with the Palphabeta GAFa domain, and the Pgamma F73-I87 C-terminus interacts with the Palphabeta catalytic domain, indicating a linear and extended interaction between Pgamma and Palphabeta. Pgamma may interact with Palpha and Pbeta simultaneously
additional information
-
isoform PDE5 is associated with protein phosphatase 1
additional information
-
isoform PDE6 delta subunit interacts with G protein-coupled receptor IP. Isoprenylation of IP is critical for this interaction, and overexpression of PDE6 delta subunit increases the initial internalization but facilitates the return of IP to the cell surface in presence of agonist. Depletion of PDE6 delta subunit abolishes cicaprost-induced internalization of IP
additional information
-
rod photoreceptor cGMP phosphodiesterase consists of a catalytic subunit complex, Palphabeta, and two inhibitory subunits, Pgamma. Isolation of Palphalphabetagammaagammadelta and Palphabetagammadeltadelta suggests that one C-terminus of Palphabeta is involved in the Palphabetagammagamma interaction with membranes, and that Pgamma dissociation opens another C-terminus for Pdelta, a prenyl-binding protein, binding, which may lead to the expression of high PDE activity. Extraction, isolation and analysis of diverse subunit complexes, detailed overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
PDE5 is phosphorylated at Ser92 by cyclic nucleotide-dependent protein kinases, phosphorylation activates PDE5 catalytic site independently of cGMP binding to the allosteric sites
phosphoprotein
O76074
phosphorylation presumably by protein kinase A or protein kinase G
phosphoprotein
-
protein kinase G-mediated phosphorylation up-regulates activity, PP1 phosphatase-mediated dephosphorylation down-regulates activity
side-chain modification
-
PDE5 is phosphorylated at Ser102 by cyclic nucleotide-dependent protein kinases, phosphorylation activates PDE5 catalytic site independently of cGMP binding to the allosteric sites
phosphoprotein
-
activation of isoform PDE5 by phosphorylation. PDE5 is dephosphorylated by the catalytic subunit of protein phosphatase 1 but not protein phosphatase 2A
phosphoprotein
-
suPDE5 activity is regulated by phosphorylation. In vitro dephosphorylation of suPDE5 decreases activity by 50%
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
chimaeric PDE5/PDE6 catalytic domain complexed with sildenafil or 3-isobutyl-1-methylxanthine and the Pgamma-inhibitory peptide Pgamma70-87, hanging drop vapor diffusion method, using 100 mM Tris (pH 8.5), 200 mM MgSO4, 12% (w/v) PEG-3350, and 2.5% (v/v) ethanol, at 4C
-
GAF A domain of PDE6C, sitting drop vapour diffusion method, using 1.5-1.8 M ammonium sulfate, 0.1 M sodium acetate, pH 4.5-5.0
-
crystals of PDE5A1 complexed with the inhibitors sildenafil, tadalafil or vardenafil, PDE5A1-inhibitor complex crystals are grown at 4C by hanging-drop vapour diffusion, adding 0.001 ml protein solution containing 10 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 100 mM NaCl and 5 mM dithiothreitol, to 0.001 ml well solution consisting of 100 mM Tris-HCl, pH 7.2-7.5, 200 mM MgCl2 and 6-9% polyethylene glycol 8000, crystals diffract to 2.3-2.8 A
-
hanging drop method, PDE5A1 in complex with the nonselective inhibitor 3-isobutyl-1-methylxanthine
-
molecular dynamics simulations based on crystal structure PDB code 1RKP. The second bridging ligand in the active site is HO- rather than H2O, serving as a nucleophile to initialize the catalytic hydrolysis of cGMP
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
5 mM beta-mercaptoethanol and bovine serum albumin
-
mercaptoethanol, stabilization
-
traysylol, protease inhibitor, stabilization
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 10 mM morpholinopropanesulfonic acid, 1.5 mM MgCl2, 0.1 mM phenylmethylsulfonyl fluoride, 1 mM dithiothreitol, 50% glycerol, pH 7.5, more than 6 months
-
-20C, 40% glycerol, 10 mM MOPS, 2 mM MgCl2, 1 mM dithiothreitol, at pH 7.5
-
-20C, purified isoenzyme PDE6R and PDE6C can be stored for several months with minimal loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion exchange chromatography
-
expression of isoform PDE6 gamma-subunit in Escherichia coli, preparation of homogeneous and isotopically labeled protein for NMR analysis
-
Ni-NTA agarose column chromatography
-
NiSO4-charged His-bind resin column chromatography and benzamidine Sepharose column chromatography
-
recombinant PDE5
-
retinal isoenzymes PDE6R form retinal rods and PDE6C from retinal cones
-
Mono Q, partially purified
-
partially purified by Q-Sepharose column chromatography
-
partially purified
-
epoxy-Sepharose cGMP affinity resin column chromatography
-
chitin column chromatography
-
immunoprecipitation with Dynabeads with Protein G
-
Mono Q, partially purified
-
Ni-NTA agarose column chromatography
-
recombinant catalytic domain of PDE5A1
-
Mono Q, gel filtration, partially purified from N18TG2 and NG108-15 neuroblastoma cells
-
purified without addition of cAMP or cGMP by Superose-12 gel filtration
Q8CG03
Mono Q, partially purified
-
DEAE-Sepharose, Blue-Sepharose, calmodulin-conjugated Sepharose, partially purified
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculovirus-expressed PDE5 in Sf9 cells
-
chimaeric PDE5/PDE6 catalytic domain is expressed in Escherichia coli BL21-codon plus cells
-
expression in Escherichia coli
-
expression in Sf9 system
-
expression of isoform PDE6 gamma-subunit in Escherichia coli as an intein-fusion with chitin binding domain. Preparation of homogeneous and isotopically labeled protein for NMR analysis
-
expression of PDE5 in Sf9 insect cells
-
expression of DdPDE3 catalytic domain in Escherichia coli and Dictyostelium
-
expression of PdeD-YFP fusion protein in Escherichia coli and Dictyostelium
Q8MLZ3
expression in Drosophila S2 cells
-
generation of transgenic animals with targeted expression of DmPDE6 to tubule type I (principal) cells. This reveals localization of DmPDE6 primarily at the apical membranes. Overexpression of DmPDE6 results in elevated cG-PDE activity and decreased tubule cGMP content. Such targeted overexpression of DmPDE6 creates phenotype that manifests itself in inhibition of the active transport and efflux of cGMP by tubules
-
expressed in Escherichia coli BL21(DE3) cells
-
expression in Escherichia coli
-
cloning of cDNA, expression of PDE5A GAF domain in Escherichia coli
-
cloning of cDNA, expression of PDE9A5 in HEK293 cells
O76083
cloning of cGMP-binding domain and expression as GST-fusion protein in Escherichia coli
-
cloning of rod PDE6 alpha and beta subunits and cone PDE6alpha', expression in Sf9 cells
-
ectopic expression of the enhanced green fluorescent protein fusion protein of human cone PDE6C in rods of transgenic Xenopus laevis
-
expressed in Escherichia coli
-
expression of his-tagged protein in baculovirus/Sf9 system
O76074
expression of isoform PDE5A1 in COS-7 cells
-
expression of PDE isoenzymes PDEA1, PDEA2 and PDEA3 in COS-7 cells
-
expression of the catalytic domain of PDE5A1 in Escherichia coli
-
fusion protein of wild-type and mutant F163A GAFa domain of enzyme to Green Fluorescent Protein or Renilla luciferase
-
splice variants PDE5A1 and PDE5A2
O76074
overexpression of enzyme gamma subunit in mouse
-
expression in Escherichia coli
Q2V2M6
cloning of EST
Q8QZV1
catalytic domain (COOH-terminal half-containing the catalytic domain Thr540-Ile949), expression in bacteria
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the expression levels of PDE5 mRNA in the tail artery are significantly decreased in orchidectomized male mice to 31.8% of the levels in sham-operated male mice
-
isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
-
nitroglycerin tolerance may involve an increased activity of PDE5
-
angiotensin II induces PDE5 expression in vitro
-
angiotensin II induces PDE5 expression in vitro
Rattus norvegicus Sprague-Dawley
-
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C68A
-
expression of isoform PDE6 wild-type and mutant C68A gamma-subunit in Escherichia coli, preparation of homogeneous and isotopically labeled protein for NMR analysis
D644A
-
10% and 4% of maximal activity in the absence of Mn2+ and Mg2+, respectively
D714A
-
33% and 22% of maximal activity in the absence of Mn2+ and Mg2+, respectively
D754A
-
59% and 28% of maximal activity in the absence of Mn2+ and Mg2+, respectively
E632A
-
20% and 16% of maximal activity in the absence of Mn2+ and Mg2+, respectively
E672A
-
3% and 8% of maximal activity in the absence of Mn2+ and Mg2+, respectively
H603A
-
38% and 22% of maximal activity in the absence of Mn2+ and Mg2+, respectively
H607A
-
3.9% and 13% of maximal activity in the absence of Mn2+ and Mg2+, respectively
H643A
-
3% and less than 1% of maximal activity in the absence of Mn2+ and Mg2+, respectively
H647A
-
less than 1% of maximal activity in the absence of Mn2+ and Mg2+, respectively
N604A
-
less than 2% of maximal activity in the absence of Mn2+ and Mg2+, respectively
N661A
-
the substitution moderately increases the Km value for cGMP hydrolysis but it markedly decreases the potency of PDE5/6cd inhibition by Pgamma inhibitory peptide
C1128S
-
the unprenylated mutant enzyme is mainly localized to the cytosol
D166A
-
mutation reduces cGMP affinity
D169A
-
mutant enzyme shows no binding of cGMP
E124A
-
mutation reduces cGMP affinity
F123A
-
mutant enzyme shows no binding of cGMP
F123W
-
mutant enzyme shows no binding of cGMP
F123Y
-
mutation reduces cGMP affinity
K170A
-
mutation reduces cGMP affinity
S165A
-
mutation reduces cGMP affinity
S97A
-
mutation reduces cGMP affinity
T172A
-
mutant enzyme shows no binding of cGMP
T175A
-
mutation reduces cGMP affinity
T176A
-
mutant enzyme shows no binding of cGMP
D299A
-
mutation in GAF-domain, no change in cGMP binding affinity
F163A
-
mutantion in GAFa domain of enzyme, mutant is unable to bind cGMP
F205A
-
mutation in GAF-domain, no cGMP binding
F205Q
-
mutation in GAF-domain, no cGMP binding
F786A
O76074
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
F820A
O76074
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
H613A
O76074
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
L765A
O76074
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Q817A
O76074
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
V782A
O76074
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Y612A
O76074
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Y612F
O76074
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
D196A
Q8CG03
the mutation disrupts cGMP binding and increases cAMP affinity in constructs containing only GAF (mammalian cGMP-dependent PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA), causing an altered cAMP-bound structural conformation
H620Q
-
the mutant shows reduced PDE6 activity that may result in an increased Ca2+ to promote photoreceptor death
H620Q
Mus musculus C57BL/6J
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generation of Pde6bH620Q mice as mouse model, knockdown of guanylate cyclase and cGMP-gated Na+/Ca2+ channels, phenotype compared to control C57BL/6J mice, overview
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D762A
Q2V2M6
mutant protein shows no cGMP hydrolytic activity
G788A
Q2V2M6
mutant enzyme retains cGMP hydrolytic activity, KM-value is nearly identical to wild-type value, the IC50-value for zaprinast is 1.5fold higher than wild-type value
H675A
-
9% and 4% of maximal activity in the absence of Mn2+ and Mg2+, respectively
additional information
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expression of isoform PDE6 wild-type and mutant C68A gamma-subunit in Escherichia coli, preparation of homogeneous and isotopically labeled protein for NMR analysis
H620Q
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generation of Pde6bH620Q mice as mouse model, knockdown of guanylate cyclase and cGMP-gated Na+/Ca2+ channels, phenotype compared to control C57BL/6J mice, overview
additional information
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overexpression of PDE6 gamma subunit in rod photoreceptors decreases the rate of rise of the rod response at dim intensities and also produces a marked acceleration in the falling phase of the light response and more rapid recovery of sensitivity and circulating current after prolonged light exposure
additional information
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introduction of a modified Pde6g gene for PDE6gamma into a line of Pde6gtm1/Pde6gtm1 mice that do not express PDE6gamma. The resulting ILE86TER mutant mice have a PDE6gamma that lacks the two final carboxyl-terminal Ile86 and Ile87 residues, a mutation that reduces inhibition by PDE6gamma. ILE86TER rods show a decreased sensitivity and rate of activation, and a decreased rate of decay of the photoresponse, consistent with decreased inhibition of PDE6 alpha and beta by PDE6gamma. ILE86TER mutant rods have a higher rate of spontaneous activation of PDE6 than wild-type rods
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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fusion protein of wild-type and mutant F163A GAFa domain of enzyme to Green Fluorescent Protein or Renilla luciferase for use in bioluminescence resonance energy transfer assay BRET as a biosensor of cGMP. BRET ratios of wild-type, but not mutant F163A, increase in presence of cGMP, but not cAMP
medicine
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phosphodiesterase 5 inhibition is a therapeutic strategy for erectile dysfunction
medicine
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use of PDE5 inhibitors in the trteatment of erectile dysfunction and pulmonary hypertension
medicine
-
enzyme isoform PDE5 mRNA and protein are markedly upregulated in hypertrophied human right ventricle
medicine
-
application of 10 mg vardenafil inhibits sphincter of Oddi motility in patients with suspected sphincter of Oddi dysfunction and reduces basal sphincter of Oddi pressure, without significant adverse effects
medicine
-
in end-stage congestive cardiac failure, intravenous sildenafil causes reduction in systemic and pulmonary vascular resistance, sildenafil has a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure
medicine
-
men using PDE5 inhibitors are approximately 4times more likely to report condom breakage than men not using PDE5 inhibitors
medicine
-
oral PDE-5 inhibitors are the current first-line treatment for erectile dysfunction
medicine
-
oral PDE-5 inhibitors improve erectile functioning. PDE-5 inhibitors are more effective than placebo in improving sexual intercourse success. The proportion of men with improved erections is significantly greater among those treated with PDE-5 inhibitors than with placebo
medicine
-
PDE5 inhibition is an efficacious option for the treatment of erectile dysfunction
medicine
-
PDE5 inhibitors show a potential antifibrotic affect against Peyronie's disease plaque in animal models
medicine
-
PDE5-inhibitors can improve both lower urinary tract symptoms and erectile dysfunction by targeting various points in the different pathways by increasing cGMP or blocking the effects of norepinephrine and other secondary messengers
medicine
-
phosphodiesterase type 5 inhibitors are considered first-line therapies for men with erectile dysfunction
medicine
-
the combined pharmacotherapy with impaza and PDE5 inhibitors helps to prevent and/or considerably reduces the risk of posttraumatic erectile dysfunction in men with traumas and strictures of the urethra
medicine
-
estrogen withdrawal, but not testosterone withdrawal, is a risk factor for PDE5 inhibitor-induced flushing
medicine
-
treatment of mice with vardenafil (5 mg/kg daily for 4 weeks) decreases high density lipoprotein serum levels and the number of antral follicles as well as induces lesser lipid content in luteal cells
medicine
-
pathological changes in ureteropelvic junction obstruction can be influenced by PDE5 inhibitors
medicine
Q2V2M6
the enzyme is suggested to be a potential target for the treatment of malaria
medicine
-
potential role for the PDE5 inhibitor sildenafil as an adjunct for the treatment of preterm labor
medicine
-
by blocking isoform PDE5, vardenafil may be used in bladder dysfunction by ameliorating irritative lower urinary tract symptoms
medicine
-
enzyme inhibitors can reverse the time-dependent forgetting in the object recognition test. The efficacy of the different inhibitors is dependent on the time point of administration after acquisition. Support for a role for cGMP in early stages of memory formation and for cAMP in the late stages of memory formation
medicine
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enzyme isoform PDE5 mRNA and protein are markedly upregulated in hypertrophied myocardium. Inhibition by sildenafil or MY-5445 significantly increases contractility in hypertrophied myocardium, but not in normal. Protein kinase G is suppressed in hypertrophied myocardium
medicine
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increased intrarenal isoform PDE5 level mediates the blunted natriuretic response to atrial natriuretic peptide during pregnancy and may contribute to the physiological volume expansion. Atrial natriuretic peptide causes a fall in mean arterial pressure. Intrarenal sildenafil increases the natriuretic response and the rise in fractional excretion of sodium in pregnant rats to the virgin value.
medicine
-
5 mg/kg/day sildenafil citrate administration to rats with acetic acid-induced colitis prevents lipid peroxidation, oxidant generation, cytokine production and neutrophil accumulation
medicine
-
chronic treatment with a high dose (80 mg/kg) of vardenafil protects the rat bladder from bladder outlet obstruction-induced contractile dysfunction to carbachol
medicine
-
impaired vascular cGMP signalling contributes to the development of diabetic vascular and cardiac dysfunction, which can be prevented by chronic phosphodiesterase-5 inhibition
medicine
-
inhibition of PDE5 decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension
medicine
-
inhibition of PDE5 with T0156 prevents the reduced production of cyclic GMP and relaxation in tolerant aortas in response to nitroglycerin
medicine
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PDE5 inhibition suppresses RhoA/Rho-associated kinase-mediated MMP-2 production by pulmonary artery smooth muscle cells, which may contribute to the regulation of pulmonary vascular remodelling. Thus, PDE5 inhibition may benefit patients with pulmonary hypertension through multiple mechanisms of action
medicine
-
PDE5 inhibitor sildenafil prevents indomethacin-induced small-intestinal ulceration in rats, via a nitric oxide/cGMP-dependent mechanism
medicine
-
PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle
medicine
-
peripheral administration of the cGMP-PDE inhibitor zaprinast dramatically alters the inflammatory response of astrocytes and microglia/macrophages to focal brain injury, decreases oxidative stress and neurodegeneration, and increases angiogenesis and vascular endothelial growth factor expression
medicine
-
pharmacological inhibition of PDE5 by vardenafil significantly enhances the endothelium-dependent vasorelaxation in aortic rings rats exposed to peroxynitrite. Acute PDE5-inhibition is advantageous in the treatment of endothelial dysfunction induced by disturbed nitric oxide-cGMP pathway due to nitro-oxidative stress
medicine
-
phosphodiesterase-5 inhibitors promote nitric oxide activity and enhance vasodilation. Infusion of PDE5 inhibitor sildenafil alone reduceds systemic and pulmonary artery blood pressure, while maintaining cardiac output and oxygen delivery. Combined hemoglobin-based oxygen carriers and sildenafil infusion results in stable systemic blood pressure, cardiac output, and oxygen delivery
molecular biology
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convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE5, convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE6, convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE9