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Literature summary for 7.6.2.2 extracted from

  • Namanja, H.A.; Emmert, D.; Pires, M.M.; Hrycyna, C.A.; Chmielewski, J.
    Inhibition of human P-glycoprotein transport and substrate binding using a galantamine dimer (2009), Biochem. Biophys. Res. Commun., 388, 672-676.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 7.6.2.2

Application

Application Comment Organism
medicine the human multidrug resistance transporter P-glycoprotein (P-gp) prevents the entry of compounds into the brain by an active efflux mechanism at the blood-brain barrier. In treatment of neurodegenerative diseases the development of new reversible inhibitors of P-gp is pertinent to overcome this problem. Design and synthesis of a crosslinked agent based on the Alzheimer’s disease treatment galantamine (Gal-2, bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate) that inhibits P-gp-mediated efflux from cultured cells. Gal-2 inhibits the efflux of the fluorescent P-gp substrate rhodamine 123 in cancer cells that over-express P-gp. It inhibits the efflux of therapeutic substrates of P-gp, such as doxorubicin, daunomycin and verapamil. Potential role of Gal-2, as inhibitors of P-gp at the blood-brain barrier to augment treatment of neurodegenerative diseases Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression in Sf9 cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate galactamine dimer. the inhibitory activity of the inhibitor on P-gp transport of substrate is evaluated in cells that over-express P-gp Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the human multidrug resistance transporter P-glycoprotein prevents the entry of compounds into the brain by an active efflux mechanism at the blood-brain barrier ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O + daunomycin/in
-
 Homo sapiens ADP + phosphate + daunomycin/out
-
 ?
ATP + H2O + doxorubicin/in
-
 Homo sapiens ADP + phosphate + doxorubicin/out
-
 ?
ATP + H2O + rhodamine 123/in
-
 Homo sapiens ADP + phosphate + rhodamine 123/out
-
 ?
ATP + H2O + verapamil/in
-
 Homo sapiens ADP + phosphate + verapamil/out
-
 ?
additional information the human multidrug resistance transporter P-glycoprotein prevents the entry of compounds into the brain by an active efflux mechanism at the blood-brain barrier Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
P-glycoprotein
-
 Homo sapiens
P-gp
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0003
-
 22°C, pH 7.4, inhibition of verapamil efflux in MCF-7/DX1 (breast adenocarcinoma) cells that over-express P-gp Homo sapiens bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate
0.0005
-
 22°C, pH 7.4, inhibition of doxorubicin efflux in MCF-7/DX1 (breast adenocarcinoma) cells that over-express P-gp Homo sapiens bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate
0.0006
-
 22°C, pH 7.4, inhibition of rhodamine 123 efflux in MCF-7/DX1 (breast adenocarcinoma) cells that over-express P-gp Homo sapiens bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate
0.0016
-
 22°C, pH 7.4, inhibition of daunomycin efflux in MCF-7/DX1 (breast adenocarcinoma) cells that over-express P-gp Homo sapiens bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate

General Information

General Information Comment Organism
physiological function the human multidrug resistance transporter P-glycoprotein prevents the entry of compounds into the brain by an active efflux mechanism at the blood-brain barrier Homo sapiens