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Information on EC 3.1.4.35 - 3',5'-cyclic-GMP phosphodiesterase and Organism(s) Homo sapiens and UniProt Accession O76074

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EC Tree
     3 Hydrolases
         3.1 Acting on ester bonds
             3.1.4 Phosphoric-diester hydrolases
                3.1.4.35 3',5'-cyclic-GMP phosphodiesterase
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UNIPROT: O76074 not found.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
phosphodiesterase type 5, phosphodiesterase-5, pde-5, phosphodiesterase 5, cgmp phosphodiesterase, pde5a, cyclic gmp phosphodiesterase, phosphodiesterase type-5, pde6b, cgmp-phosphodiesterase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cGMP-binding cGMP-specific phosphodiesterase
-
cGMP-specific PDE5
-
cGMP-specific PDE5A1
-
PDE5A
phosphodiesterase 5
-
3',5'-cyclic GMP phosphodiesterase
-
-
-
-
cGMP 3',5'-cyclic phosphodiesterase subunit delta
-
-
cGMP phosphodiesterase
-
-
-
-
cGMP phosphodiesterase 6
-
-
cGMP-binding cGMP specific phosphodiesterase
-
-
cGMP-binding cGMP-specific phosphodiesterase
-
-
cGMP-PDE
cGMP-phosphodiesterase
-
-
cGMP-phosphodiesterase-5
-
-
cGMP-specific PDE
-
-
cGMP-specific phosphodiesterase
-
-
cGMP-specific phosphodiesterase-5
-
-
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
-
-
-
-
PDE-6
-
-
PDE4
-
-
PDE5A1
PDE6AB
-
isoform
PDE6C
-
isoform
PDE6D
-
-
PDE9A
PDEdelta
-
-
PDEgamma
-
PDE6 inhibitory gamma-subunit, PDEgamma keeps PDE6 inactive by binding tightly to the catalytic alpha,beta-subunits in the dark
phospho-diesterase-5
-
-
phosphodiesterase 5
-
-
phosphodiesterase 9
-
-
phosphodiesterase cGMP
-
-
-
-
phosphodiesterase type 5
-
-
phosphodiesterase type-5
-
-
phosphodiesterase, guanosine cyclic 3',5'-phosphate
-
-
-
-
phosphodiesterase-5
-
-
phosphodiesterase-6
-
-
PrBP/delta
-
-
type 5 phosphodiesterase
-
-
type 9 cGMP-specific phosphodiesterase
-
type-5 phosphodiesterase
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-GMP 5'-nucleotidohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9068-52-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
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'-cGMP + H2O
5'-GMP
show the reaction diagram
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
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
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
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
slight activation of PDE9A1
Mn2+
required for activity, maximal activity at approx. 10 mM
Zn2+
-
approx. 2.5 fold activation at 0.01 mM, strong inhibition above
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1R,3S)-2-acetyl-1-(2H-1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-b-carboline-3-carboxylate
ZINC03024617
(1S,3R)-2-acetyl-1-(2H-1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-b-carboline-3-carboxylate
ZINC03024615
(1S,3S,4aS,9aR)-1-(2H-1,3-benzodioxol-5-yl)-2-(chloroacetyl)-2,3,4,4a,9,9a-hexahydro-1H-b-carboline-3-carboperoxoic acid
ZINC21986065
(2R)-4-[(2H-1,3-benzodioxol-5-yl)methyl]-1-(3-methoxybenzoyl)-N-methylpiperazine-2-carboxamide
ZINC24891165
(2R)-N-[[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-(methylsulfanyl)butanamide
ZINC32995888
(2S)-N-[[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-(methylsulfanyl)butanamide
ZINC32995890
(3R)-1-(2H-1,3-benzodioxole-5-carbonyl)-4-(2-methoxyphenyl)-N-[(pyridin-3-yl)methyl]pyrrolidine-3-carboxamide
ZINC36055139
(3S)-N-[(2,3-dihydro-1,4-benzodioxin-6-yl)methyl]-2-(furan-2-carbonyl)-N-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
ZINC23055991
(6R,12aR)-2-propyl-6-(3,4,5-trimethoxyphenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC02092043
(6R,12aR)-6-(2H-1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC12360812
(6R,12aR)-6-(4-ethoxy-3-methoxyphenyl)-2-(2-methylpropyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC15955458
(6R,12aS)-2-methyl-6-(3,4,5-trimethoxyphenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
(6R,12aS)-2-propyl-6-(3,4,5-trimethoxyphenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC11692256
(6R,12aS)-6-(4-ethoxy-3-methoxyphenyl)-2-(3-methylbutyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC02120502
(6S,12aR)-2-benzyl-6-(3,4-dimethoxyphenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC16043001
(6S,12aS)-2-methyl-6-(3,4,5-trimethoxyphenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC02093785
(6S,12aS)-2-[(furan-2-yl)methyl]-6-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC00490454
(6S,12aS)-2-[2-(3,4-dimethoxyphenyl)ethyl]-6-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC26772005
(6S,12aS)-6-(2H-1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
ZINC08204637
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-[(3R)-1-(2H-1,3-benzodioxol-5-yl)-5-oxopyrrolidine-3-carbonyl]-N-(4-methoxyphenyl)-L-prolinamide
ZINC40146722
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-[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
3-isobutyl-1-methylxanthine
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
dipyridamole
PDE5 is specifically inhibited by dipyridamole
methyl 2-[(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylate
ZINC29158966
N-[(1S)-1-[1-(2H-1,3-benzodioxole-5-carbonyl)piperidin-4-yl]-2-oxo-2-(pyrrolidin-1-yl)ethyl]-2-methylbenzamide
ZINC36210867
N-[(S)-[(3R)-1-(2H-1,3-benzodioxole-5-carbonyl)piperidin-3-yl](pyridin-2-yl)methyl]acetamide
ZINC19020327
N-[[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-4-(2,5-dioxopyrrolidin-1-yl)-N-methylbenzamide
ZINC23183710
sildenafil citrate
inhibition of PDE5 activity in the intestine, which might occur during sildenafil citrate ingestion, could result in a transitory diarrhoe
tadalafil
-
[4-[(1S,2S)-2-(2H-1,3-benzodioxol-5-yl)cyclopropane-1-carbonyl]piperazin-1-yl](1H-indol-2-yl)methanone
ZINC44448076
[4-[(1S,2S)-2-(2H-1,3-benzodioxol-5-yl)cyclopropane-1-carbonyl]piperazin-1-yl](1H-indol-3-yl)methanone
ZINC44448130
(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
(E)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone O-carbamoyl oxime
-
filaminast
1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
-
-
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-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-benzyl-2-[4-[2-(2-phenyl-1H-benzimidazol-1-yl)ethoxy]phenyl]-1H-benzimidazole
-
-
1-benzyl-2-[4-[2-cyclohexyl-2-(2-phenyl-1H-benzimidazol-1-yl)ethoxy]phenyl]-1H-benzimidazole
-
-
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
-
-
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-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-methoxy-7-methyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazin-6(5H)-one
-
-
2-[1-(2,4-dichlorobenzyl)-2-methyl-5-(methylmercapto)-1H-indol-3-yl] ethanaminium chloride
-
IC50: 0.002 mM, PDE5
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
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
-
-
3-(cyclopentylmethoxy)-N-(2,6-dichlorophenyl)-4-methoxybenzamide
-
piclamilast
3-(cyclopropylmethoxy)-N-(2,6-dichlorophenyl)-4-(difluoromethoxy)benzamide
-
roflumilast
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-methylxanthine
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-[(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
-
-
4-(1,3-benzodioxol-5-ylmethoxy)-2-(1H-imidazol-1-yl)-5-phenylpyrimidine
-
-
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)-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-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
-
-
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
-
-
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
avanafil
-
TA-1790, highly selective inhibitor of PDE5
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
chamomile
-
weak, but still statistically significant inhibition of PDE5A1
Cilostamide
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
-
-
deltarasin
-
-
deltazinone 1
-
-
dipyridamole
EDTA
0.5 mM, 35% inhibition of activity in the absence of a divalent metal ion
Evo48
-
potent inhibitor of PDE5
-
exisulind
-
-
ginkgetin
-
IC50: 0.00059 mM
malvidin
-
IC50: 0.0354 mM
malvidin-3-O-beta-glucoside
-
IC50: 0.0116 mM
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
-
-
peonidin
-
-
peonidin 3-glucoside
-
-
petunidin
-
-
petunidin 3-glucoside
-
-
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
-
RP-73401
-
IC50: 0.0089 mM, PDE5
SCH 51866
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
SLx-2101
-
inhibits excellent potency both ex vivo and in vivo
tadalafil
trans-4-([2-[(3-chloro-4-methoxyphenyl)carbamoyl]-4-cyanophenyl]carbamoyl)cyclohexanecarboxylic acid
-
-
udenafil
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
zaprinast
Zn2+
-
strong inhibition above 0.01 mM, almost complete inhibition at 0.1 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cGMP
activation by suggested binding to PDE5 GAF domain
Escherichia coli stable toxin
possibly due to an increase in cGMP resulting from stable toxin treatment
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0029 - 0.182
cGMP
0.0247 - 0.0651
2'-O-anthraniloyl-cGMP
0.065
3',5'-cGMP
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
0.00025 - 0.0062
cGMP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00083 - 3.8
cGMP
4400
3',5'-cGMP
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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 - 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
0.0000487 - 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
0.01212 - 0.09485
3-isobutyl-1-methylxanthine
0.0000173 - 0.001605
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
0.0000026 - 0.0000183
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
0.078 - 0.14
cone Pgamma subunit
-
0.0000035 - 0.0001735
E4021
0.105 - 0.155
rod Pgamma subunit
-
0.000013 - 0.0000984
sildenafil
0.0001778 - 0.01438
zaprinast
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000019 - 0.000327
3-isobutyl-1-methylxanthine
0.0000013 - 0.000235
sildenafil
0.0000022 - 0.000301
tadalafil
0.00000006 - 0.0000613
vardenafil
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
Homo sapiens
-
IC50: 0.00067 mM, PDE5
0.053
(E)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone O-carbamoyl oxime
Homo sapiens
-
-
0.019
1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
Homo sapiens
-
-
0.000055
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
Homo sapiens
-
i.e. BAY 73-6691, IC50: 55 nM
0.0000004
1-(2-ethoxyethyl)-3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens
-
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
Homo sapiens
-
-
0.0000037
1-[4-[(1,3-benzodioxol-5-ylmethyl)amino]-6-chloroquinazolin-2-yl]piperidine-4-carboxylic acid
Homo sapiens
-
-
0.00069
2,2',2'',2'''-[(4,8-dipiperidin-1-ylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
Homo sapiens
-
-
0.000005
2-(2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
Homo sapiens
-
-
0.00001
2-(2-propoxyphenyl)-1,7-dihydro-6H-purin-6-one
Homo sapiens
-
-
0.0000017
2-(5-amino-2-propoxyphenyl)thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.0000065
2-(5-[[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl]-2-propoxyphenyl)-5-methylquinazolin-4(3H)-one
Homo sapiens
-
-
0.00001
2-methoxy-7-methyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazin-6(5H)-one
Homo sapiens
-
-
0.002
2-[1-(2,4-dichlorobenzyl)-2-methyl-5-(methylmercapto)-1H-indol-3-yl] ethanaminium chloride
Homo sapiens
-
IC50: 0.002 mM, PDE5
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
Homo sapiens
-
-
0.0035
3-(cyclopentylmethoxy)-N-(2,6-dichlorophenyl)-4-methoxybenzamide
Homo sapiens
-
-
0.017
3-(cyclopropylmethoxy)-N-(2,6-dichlorophenyl)-4-(difluoromethoxy)benzamide
Homo sapiens
-
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
pH and temperature not specified in the publication
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
pH and temperature not specified in the publication
0.000014
4-(1,3-benzodioxol-5-ylmethoxy)-2-(1H-imidazol-1-yl)-5-phenylpyrimidine
Homo sapiens
-
-
0.053
4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylic acid
Homo sapiens
-
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
-
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
Homo sapiens
-
-
0.0117
amentoflavone
Homo sapiens
-
IC50: 0.0117 mM
0.0000011 - 0.00002
benzamidenafil
0.00152
bilobetin
Homo sapiens
-
IC50: 0.00152 mM
0.0000405 - 0.006
Cilostamide
0.0000109
dipyridamole
Homo sapiens
-
bladder homogenate, 30°C, pH 7.0
0.00059
ginkgetin
Homo sapiens
-
IC50: 0.00059 mM
0.0354
malvidin
Homo sapiens
-
IC50: 0.0354 mM
0.0116
malvidin-3-O-beta-glucoside
Homo sapiens
-
IC50: 0.0116 mM
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
Homo sapiens
-
-
0.000003
N-[3-(1,3-dimethyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-propoxyphenyl]methanesulfonamide
Homo sapiens
-
-
0.0000035
N-[3-(4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]piperidine-1-carboxamide
Homo sapiens
-
-
0.000018
N-[3-(4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]morpholine-4-carboxamide
Homo sapiens
-
-
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
Homo sapiens
-
pH and temperature not specified in the publication
0.000021
quinazolinamine
Homo sapiens
-
IC50: 0.000021 mM, PDE5
0.0089
RP-73401
Homo sapiens
-
IC50: 0.0089 mM, PDE5
0.00324
sciadopitysin
Homo sapiens
-
IC50: 0.00324 mM
0.0199
sequoiaflavone
Homo sapiens
-
IC50: 0.0199 mM
0.0000016 - 0.01
sildenafil
0.0000018 - 0.01
tadalafil
0.0000004
trans-4-([2-[(3-chloro-4-methoxyphenyl)carbamoyl]-4-cyanophenyl]carbamoyl)cyclohexanecarboxylic acid
Homo sapiens
-
-
0.0000003 - 0.00337
vardenafil
0.0000088
zaprinast
Homo sapiens
-
bladder homogenate, 30°C, pH 7.0
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.5
-
almost no activity at pH 6.0 and 8.5, respectively
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum
Manually annotated by BRENDA team
very low expression level
Manually annotated by BRENDA team
colonic T84 cells
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
-
PDE5
Manually annotated by BRENDA team
-
colon cancer cell
Manually annotated by BRENDA team
-
muscle fibers of bladder
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
-
PFE9A gene expression is higher in reticulocytes from sickle cell disease individuals compared to control cells
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
PDE5
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
splice variant PDE9A5
Manually annotated by BRENDA team
splice variant PDE9A1
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
physiological function
-
subunit PDEdelta is a prenyl binding protein that is essential for the shuttling of small GTPases between different membrane compartments and, thus, for their proper functioning. Farnesylated 2',3'-cyclic-nucleotide 3'-phosphodiesterase, RAB23, CDC42 and CNP are PDEdelta-interacting proteins. Subunit PDEdelta also associates with the lamin A mutant progerin in a prenyl-dependent manner
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PDE5A_HUMAN
875
0
99985
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
105000
2 * 105000, immunoblot
200000
gel filtration
99000
x * 99000, SDS-PAGE of recombinant His-tagged protein
125000
-
recombinant enhanced green fluorescent protein fusion protein of human cone PDE6C
72000
-
PDE9, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 99000, SDS-PAGE of recombinant His-tagged protein
dimer
2 * 105000, immunoblot
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of PDE5A1 complexed with the inhibitors sildenafil, tadalafil or vardenafil, PDE5A1-inhibitor complex crystals are grown at 4°C 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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F163A
mutantion in GAFa domain of enzyme, mutant is unable to bind cGMP
F786A
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
F820A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
H613A
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
L765A
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Q817A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
V782A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Y612A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Y612F
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
D299A
-
mutation in GAF-domain, no change in cGMP binding affinity
F205A
-
mutation in GAF-domain, no cGMP binding
F205Q
-
mutation in GAF-domain, no cGMP binding
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant catalytic domain of PDE5A1
chitin column chromatography
-
GSH-Sepharose column chromatography and Superdex 75 gel filtration
-
immunoprecipitation with Dynabeads with Protein G
-
Mono Q, partially purified
-
Ni-NTA agarose column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of his-tagged protein in baculovirus/Sf9 system
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
cloning of cDNA, expression of PDE5A GAF domain in Escherichia coli
-
cloning of cDNA, expression of PDE9A5 in HEK293 cells
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
-
expressed in Escherichia coli RosettaTM2 cells
-
expression of isoform PDE5A1 in COS-7 cells
-
expression of PDE isoenzymes PDEA1, PDEA2 and PDEA3 in COS-7 cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lin, C.S.; Lau, A.; Tu, R.; Lue, T.F.
Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum
Biochem. Biophys. Res. Commun.
268
628-635
2000
Homo sapiens
Manually annotated by BRENDA team
Liu, L.; Underwood, T.; Li, H.; Pamukcu, R.; Thompson, W.J.
Specific cGMP binding by the cGMP binding domains of cGMP-binding cGMP specific phosphodiesterase
Cell. Signal.
14
45-51
2002
Homo sapiens
Manually annotated by BRENDA team
Sopory, S.; Kaur, T.; Visweswariah, S.S.
The cGMP-binding, cGMP-specific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion
Cell. Signal.
16
681-692
2004
Homo sapiens (O76074), Homo sapiens
Manually annotated by BRENDA team
Sopory, S.; Balaji, S.; Srinivasan, N.; Visweswariah, S.S.
Modeling and mutational analysis of the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5
FEBS Lett.
539
161-166
2003
Homo sapiens
Manually annotated by BRENDA team
Wang, P.; Wu, P.; Egan, R.W.; Billah, M.M.
Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants
Gene
314
15-27
2003
Homo sapiens (O76083), Homo sapiens
Manually annotated by BRENDA team
O'Grady, S.M.; Jiang, X.; Maniak, P.J.; Birmachu, W.; Scribner, L.R.; Bulbulian, B.; Gullikson, G.W.
Cyclic AMP-dependent Cl secretion is regulated by multiple phosphodiesterase subtypes in human colonic epithelial cells
J. Membr. Biol.
185
137-144
2002
Homo sapiens
Manually annotated by BRENDA team
Wang, P.; Wu, P.; Myers, J.G.; Stamford, A.; Egan, R.W.; Billah, M.M.
Characterization of human, dog and rabbit corpus cavernosum type 5 phosphodiesterases
Life Sci.
68
1977-1987
2001
Canis lupus familiaris, Oryctolagus cuniculus, Homo sapiens
Manually annotated by BRENDA team
Sung, B.J.; Hwang, K.Y.; Jeon, Y.H.; Lee, J.I.; Heo, Y.S.; Kim, J.H.; Moon, J.; Yoon, J.M.; Hyun, Y.L.; Kim, E.; Eum, S.J.; Park, S.Y.; Lee, J.O.; Lee, T.G.; Ro, S.; Cho, J.M.
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules
Nature
425
98-102
2003
Homo sapiens (O76074), Homo sapiens
Manually annotated by BRENDA team
Burnett, A.L.
Phosphodiesterase 5 mechanisms and therapeutic applications
Am. J. Cardiol.
96
29M-31M
2005
Homo sapiens
Manually annotated by BRENDA team
Dolci, S.; Belmonte, A.; Santone, R.; Giorgi, M.; Pellegrini, M.; Carosa, E.; Piccione, E.; Lenzi, A.; Jannini, E.A.
Subcellular localization and regulation of type-1C and type-5 phosphodiesterases
Biochem. Biophys. Res. Commun.
341
837-846
2006
Homo sapiens
Manually annotated by BRENDA team
Zhang, J.; Kuvelkar, R.; Wu, P.; Egan, R.W.; Billah, M.M.; Wang, P.
Differential inhibitor sensitivity between human recombinant and native photoreceptor cGMP-phosphodiesterases (PDE6s)
Biochem. Pharmacol.
68
867-873
2004
Homo sapiens
Manually annotated by BRENDA team
Bischoff, E.
Potency, selectivity, and consequences of nonselectivity of PDE inhibition
Int. J. Impot. Res.
16
S11-S14
2004
Bos taurus, Homo sapiens, Bos taurus PDE6
Manually annotated by BRENDA team
Weeks, J.L.; Zoraghi, R.; Beasley, A.; Sekhar, K.R.; Francis, S.H.; Corbin, J.D.
High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients
Int. J. Impot. Res.
17
5-9
2005
Homo sapiens
Manually annotated by BRENDA team
Dell'Agli, M.; Galli, G.V.; Vrhovsek, U.; Mattivi, F.; Bosisio, E.
In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes
J. Agric. Food Chem.
53
1960-1965
2005
Homo sapiens
Manually annotated by BRENDA team
Huai, Q.; Liu, Y.; Francis, S.H.; Corbin, J.D.; Ke, H.
Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity
J. Biol. Chem.
279
13095-13101
2004
Homo sapiens (O76074)
Manually annotated by BRENDA team
Belmonte, A.; Ticconi, C.; Dolci, S.; Giorgi, M.; Zicari, A.; Lenzi, A.; Jannini, E.A.; Piccione, E.
Regulation of phosphodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin
J. Soc. Gynecol. Investig.
12
570-577
2005
Homo sapiens
Manually annotated by BRENDA team
Mancina, R.; Filippi, S.; Marini, M.; Morelli, A.; Vignozzi, L.; Salonia, A.; Montorsi, F.; Mondaini, N.; Vannelli, G.B.; Donati, S.; Lotti, F.; Forti, G.; Maggi, M.
Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens
Mol. Hum. Reprod.
11
107-115
2005
Oryctolagus cuniculus, Homo sapiens
Manually annotated by BRENDA team
Wunder, F.; Tersteegen, A.; Rebmann, A.; Erb, C.; Fahrig, T.; Hendrix, M.
Characterization of the first potent and selective PDE9 inhibitor using a cGMP reporter cell line
Mol. Pharmacol.
68
1775-1781
2005
Homo sapiens, Mus musculus (O70628), Mus musculus
Manually annotated by BRENDA team
Dell'Agli, M.; Galli, G.V.; Bosisio, E.
Inhibition of cGMP-phosphodiesterase-5 by biflavones of Ginkgo biloba
Planta Med.
72
468-470
2006
Homo sapiens
Manually annotated by BRENDA team
Oelke, M.; Hedlund, P.; Albrecht, K.; Ellinghaus, P.; Stief, C.G.; Jonas, U.; Andersson, K.E.; Uckert, S.
Expression of cAMP and cGMP-phosphodiesterase isoenzymes 3, 4, and 5 in the human clitoris: immunohistochemical and molecular biology study
Urology
67
1111-1116
2006
Homo sapiens
Manually annotated by BRENDA team
Waldkirch, E.; Uckert, S.; Yildirim, H.; Sohn, M.; Jonas, U.; Stief, C.G.; Andersson, K.E.; Hedlund, P.
Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries--immunohistochemical distribution and functional significance
World J. Urol.
23
405-410
2005
Homo sapiens
Manually annotated by BRENDA team
Zoraghi, R.; Francis, S.H.; Corbin, J.D.
Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors
Biochemistry
46
13554-13563
2007
Homo sapiens (O76074)
Manually annotated by BRENDA team
Biswas, K.H.; Sopory, S.; Visweswariah, S.S.
The GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) is a sensor and a sink for cGMP
Biochemistry
47
3534-3543
2008
Homo sapiens (O76074)
Manually annotated by BRENDA team
Xiong, Y.; Lu, H.T.; Li, Y.; Yang, G.F.; Zhan, C.G.
Characterization of a catalytic ligand bridging metal ions in phosphodiesterases 4 and 5 by molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations
Biophys. J.
91
1858-1867
2006
Homo sapiens (O76074)
Manually annotated by BRENDA team
Nagendran, J.; Archer, S.L.; Soliman, D.; Gurtu, V.; Moudgil, R.; Haromy, A.; St Aubin, C.; Webster, L.; Rebeyka, I.M.; Ross, D.B.; Light, P.E.; Dyck, J.R.; Michelakis, E.D.
Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility
Circulation
116
238-248
2007
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Lin, C.S.; Lin, G.; Xin, Z.C.; Lue, T.F.
Expression, distribution and regulation of phosphodiesterase 5
Curr. Pharm. Des.
12
3439-3457
2006
Homo sapiens
Manually annotated by BRENDA team
Filippi, S.; Morelli, A.; Sandner, P.; Fibbi, B.; Mancina, R.; Marini, M.; Gacci, M.; Vignozzi, L.; Vannelli, G.B.; Carini, M.; Forti, G.; Maggi, M.
Characterization and functional role of androgen-dependent PDE5 activity in the bladder
Endocrinology
148
1019-1029
2007
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Uckert, S.; Oelke, M.; Stief, C.G.; Andersson, K.E.; Jonas, U.; Hedlund, P.
Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate
Eur. Urol.
49
740-745
2006
Homo sapiens
Manually annotated by BRENDA team
Wilson, S.J.; Smyth, E.M.
Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylation-dependent interaction with the delta subunit of cGMP phosphodiesterase 6
J. Biol. Chem.
281
11780-11786
2006
Homo sapiens
Manually annotated by BRENDA team
Almeida, C.B.; Traina, F.; Lanaro, C.; Canalli, A.A.; Saad, S.T.; Costa, F.F.; Conran, N.
High expression of the cGMP-specific phosphodiesterase, PDE9A, in sickle cell disease (SCD) and the effects of its inhibition in erythroid cells and SCD neutrophils
Br. J. Haematol.
142
836-844
2008
Homo sapiens
Manually annotated by BRENDA team
Eros, D.; Szantai-Kis, C.; Kiss, R.; Keri, G.; Hegymegi-Barakonyi, B.; Koevesdi, I.; Orfi, L.
Structure-activity relationships of PDE5 inhibitors
Curr. Med. Chem.
15
1570-1585
2008
Homo sapiens
Manually annotated by BRENDA team
Santos-Silva, A.J.; Cairrao, E.; Morgado, M.; Alvarez, E.; Verde, I.
PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries
Eur. J. Pharmacol.
582
102-109
2008
Homo sapiens (O76074), Homo sapiens
Manually annotated by BRENDA team
Maschi, O.; Cero, E.D.; Galli, G.V.; Caruso, D.; Bosisio, E.; DellAgli, M.
Inhibition of human cAMP-phosphodiesterase as a mechanism of the spasmolytic effect of Matricaria recutita L
J. Agric. Food Chem.
56
5015-5020
2008
Homo sapiens
Manually annotated by BRENDA team
Reingruber, J.; Holcman, D.
Estimating the rate constant of cyclic GMP hydrolysis by activated phosphodiesterase in photoreceptors
J. Chem. Phys.
129
145102
2008
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Song, J.; Guo, L.W.; Muradov, H.; Artemyev, N.O.; Ruoho, A.E.; Markley, J.L.
Intrinsically disordered gamma-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure
Proc. Natl. Acad. Sci. USA
105
1505-1510
2008
Homo sapiens
Manually annotated by BRENDA team
Chen, C.Y.; Chang, Y.H.; Bau, D.T.; Huang, H.J.; Tsai, F.J.; Tsai, C.H.; Chen, C.Y.
Discovery of potent inhibitors for phosphodiesterase 5 by virtual screening and pharmacophore analysis
Acta Pharmacol. Sin.
30
1186-1194
2009
Homo sapiens
Manually annotated by BRENDA team
Tsertsvadze, A.; Fink, H.A.; Yazdi, F.; MacDonald, R.; Bella, A.J.; Ansari, M.T.; Garritty, C.; Soares-Weiser, K.; Daniel, R.; Sampson, M.; Fox, S.; Moher, D.; Wilt, T.J.
Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis
Ann. Intern. Med.
151
650-661
2009
Homo sapiens
Manually annotated by BRENDA team
Tollefson, M.B.; Acker, B.A.; Jacobsen, E.J.; Hughes, R.O.; Walker, J.K.; Fox, D.N.; Palmer, M.J.; Freeman, S.K.; Yu, Y.; Bond, B.R.
1-(2-(2,2,2-Trifluoroethoxy)ethyl)-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors
Bioorg. Med. Chem. Lett.
20
3125-3128
2010
Homo sapiens
Manually annotated by BRENDA team
Taylor, J.; Baldo, O.B.; Storey, A.; Cartledge, J.; Eardley, I.
Differences in side-effect duration and related bother levels between phosphodiesterase type 5 inhibitors
BJU Int.
103
1392-1395
2009
Homo sapiens
Manually annotated by BRENDA team
Cortes-Gonzalez, J.R.; Glina, S.
Have phosphodiesterase-5 inhibitors changed the indications for penile implants?
BJU Int.
103
1518-1521
2009
Homo sapiens
Manually annotated by BRENDA team
Tamimi, N.A.; Mincik, I.; Haughie, S.; Lamb, J.; Crossland, A.; Ellis, P.
A placebo-controlled study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia
BJU Int.
106
674-680
2010
Homo sapiens
Manually annotated by BRENDA team
Kim, T.E.; Kim, B.H.; Kim, J.R.; Lim, K.S.; Hong, J.H.; Kim, K.P.; Kim, H.S.; Shin, S.G.; Jang, I.J.; Yu, K.S.
Effect of food on the pharmacokinetics of the oral phosphodiesterase 5 inhibitor udenafil for the treatment of erectile dysfunction
Br. J. Clin. Pharmacol.
68
43-46
2009
Homo sapiens
Manually annotated by BRENDA team
Murthy, K.S.
Contractile agonists attenuate cGMP levels by stimulating phosphorylation of cGMP-specific PDE5; an effect mediated by RhoA/PKC-dependent inhibition of protein phosphatase 1
Br. J. Pharmacol.
153
1214-1224
2008
Homo sapiens
Manually annotated by BRENDA team
Ibishev, K.h.S.
Efficiency of combined therapy with impaza and type 5 phosphodiesterase inhibitors in prophylactics of posttraumatic erectile dysfunction
Bull. Exp. Biol. Med.
148
322-324
2009
Homo sapiens
Manually annotated by BRENDA team
Laties, A.M.
Vision disorders and phosphodiesterase type 5 inhibitors: a review of the evidence to date
Drug Saf.
32
1-18
2009
Homo sapiens
Manually annotated by BRENDA team
Koehler, T.S.; McVary, K.T.
The relationship between erectile dysfunction and lower urinary tract symptoms and the role of phosphodiesterase type 5 inhibitors
Eur. Urol.
55
38-48
2009
Homo sapiens
Manually annotated by BRENDA team
Gur, S.; Sikka, S.C.; Hellstrom, W.J.
Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress
Expert Opin. Investig. Drugs
17
855-864
2008
Homo sapiens
Manually annotated by BRENDA team
Cheon, Y.K.; Cho, Y.D.; Moon, J.H.; Im, H.H.; Jung, Y.; Lee, J.S.; Lee, M.S.; Shim, C.S.
Effects of vardenafil, a phosphodiesterase type-5 inhibitor, on sphincter of Oddi motility in patients with suspected biliary sphincter of Oddi dysfunction
Gastrointest. Endosc.
69
1111-1116
2009
Homo sapiens
Manually annotated by BRENDA team
Speranza, L.; Franceschelli, S.; Pesce, M.; Vinciguerra, I.; De Lutiis, M.A.; Grilli, A.; Felaco, M.; Patruno, A.
Phosphodiesterase type-5 inhibitor and oxidative stress
Int. J. Immunopathol. Pharmacol.
21
879-889
2009
Homo sapiens
Manually annotated by BRENDA team
Muradov, H.; Boyd, K.K.; Haeri, M.; Kerov, V.; Knox, B.E.; Artemyev, N.O.
Characterization of human cone phosphodiesterase-6 ectopically expressed in Xenopus laevis rods
J. Biol. Chem.
284
32662-32669
2009
Homo sapiens
Manually annotated by BRENDA team
Botha, P.; Parry, G.; Dark, J.H.; Macgowan, G.A.
Acute hemodynamic effects of intravenous sildenafil citrate in congestive heart failure: comparison of phosphodiesterase type-3 and -5 inhibition
J. Heart Lung Transplant.
28
676-682
2009
Homo sapiens
Manually annotated by BRENDA team
Okuyucu, S.; Guven, O.E.; Akoglu, E.; Ucar, E.; Dagli, S.
Effect of phosphodiesterase-5 inhibitor on hearing
J. Laryngol. Otol.
123
718-722
2009
Homo sapiens
Manually annotated by BRENDA team
Zou, P.; Hou, P.; Oh, S.S.; Ge, X.; Bloodworth, B.C.; Low, M.Y.; Koh, H.L.
Identification of benzamidenafil, a new class of phosphodiesterase-5 inhibitor, as an adulterant in a dietary supplement
J. Pharm. Biomed. Anal.
47
255-259
2008
Homo sapiens
Manually annotated by BRENDA team
Rybalkina, I.G.; Tang, X.B.; Rybalkin, S.D.
Multiple affinity states of cGMP-specific phosphodiesterase for sildenafil inhibition defined by cGMP-dependent and cGMP-independent mechanisms
Mol. Pharmacol.
77
670-677
2010
Homo sapiens
Manually annotated by BRENDA team
Al-Shaiji, T.F.; Brock, G.B.
Peyronies disease: evolving surgical management and the role of phosphodiesterase 5 inhibitors
ScientificWorldJournal
9
822-845
2009
Homo sapiens
Manually annotated by BRENDA team
Crosby, R.; Yarber, W.L.; Sanders, S.A.; Graham, C.A.
Is phosphodiesterase type 5 inhibitor use associated with condom breakage?
Sex. Transm. Infect.
85
404-405
2009
Homo sapiens
Manually annotated by BRENDA team
Lakics, V.; Karran, E.H.; Boess, F.G.
Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues
Neuropharmacology
59
367-374
2010
Homo sapiens (O76074), Homo sapiens (O76083)
Manually annotated by BRENDA team
Kuechler, P.; Zimmermann, G.; Winzker, M.; Janning, P.; Waldmann, H.; Ziegler, S.
Identification of novel PDEdelta interacting proteins
Bioorg. Med. Chem.
26
1426-1434
2018
Homo sapiens
Manually annotated by BRENDA team
Kay?k, G.; Tuezuen, N.?.; Durdagi, S.
Investigation of PDE5/PDE6 and PDE5/PDE11 selective potent tadalafil-like PDE5 inhibitors using combination of molecular modeling approaches, molecular fingerprint-based virtual screening protocols and structure-based pharmacophore development
J. Enzyme Inhib. Med. Chem.
32
311-330
2017
Homo sapiens (O76074)
Manually annotated by BRENDA team