Literature summary for 2.7.1.137 extracted from

Ayral-Kaloustian, S.; Gu, J.; Lucas, J.; Cinque, M.; Gaydos, C.; Zask, A.; Chaudhary, I.; Wang, J.; Di, L.; Young, M.; Ruppen, M.; Mansour, T.S.; Gibbons, J.J.; Yu, K.
Hybrid inhibitors of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR): design, synthesis, and superior antitumor activity of novel wortmannin-rapamycin conjugates (2009), J. Med. Chem., 53, 452-459.

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Application

Application	Comment	Organism
drug development	the enzyme is a target for drug design in cancer therapy. Combined targeting of PI3K and mTOR presents an opportunity for robust and synergistic anticancer efficacy	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
(1E,4S,4aR,5R,6aS,7S)-5-(acetyloxy)-1-[[[3-(dimethylamino)-propyl](methyl)amino]methylene]-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-7-yl-(1R,2R,4S)-4-[(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl]-2-methoxycyclohexyl octanedioate	-	Homo sapiens
(1E,4S,4aR,5R,6aS,7S)-5-(acetyloxy)-1-{[[3-(dimethylamino)propyl](methyl)amino]methylene}-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-7-yl-(1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl octanedioate	-	Mus musculus
(1E,4S,4aR,5R,6aS,7S,9aR)-1-({[3-(dimethylamino)propyl](methyl)amino}methylidene)-7,11-dihydroxy-4-(methoxymethyl)-4a,6a,9a-trimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate	-	Mus musculus
(1Z,4S,4aR,6aS,9aR)-1-([[3-(dimethylamino)propyl](methyl)amino]methylidene)-5-ethoxy-7,11-dihydroxy-4-(methoxymethyl)-4a,6a-dimethyl-4a,5,6,6a,7,8,9,9a-octahydroindeno[4,5-h]isochromene-2,10(1H,4H)-dione	-	Homo sapiens
(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-[(2R)-1-[(1S,3R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone	-	Homo sapiens
(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R)-3-hydroxycyclohexyl]propan-2-yl}-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone	-	Mus musculus
17-hydroxywortmannin	-	Homo sapiens
17-hydroxywortmannin	-	Mus musculus
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	i.e. LY294002	Homo sapiens
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	i.e. LY294002	Mus musculus
additional information	drug design and synthesis, 17-hydroxywortmannin analogues conjugated to rapamycin analogues via a prodrug linker , inhibitory potency, overview	Homo sapiens
PWT-458	i.e. poly(oxy-1,2-ethanediyl)-, R-[2-[[2-[[(1S,6bR,9S,9aS,11R,11bR)-11-(acetyloxy)-1,6,6b,7,8,9,9a,10,11,11b-decahydro-1-(methoxymethyl)-9a,11b-dimethyl-3,6-dioxo-3Hfuro[4,3,2-de]indeno[4,5-h]-2-benzopyran-9-yl]oxy]-2-oxoethyl]thio]ethyl]-omega-methoxy	Homo sapiens
PWT-458	i.e. poly(oxy-1,2-ethanediyl)-, R-[2-[[2-[[(1S,6bR,9S,9aS,11R,11bR)-11-(acetyloxy)-1,6,6b,7,8,9,9a,10,11,11b-decahydro-1-(methoxymethyl)-9a,11b-dimethyl-3,6-dioxo-3Hfuro[4,3,2-de]indeno[4,5-h]-2-benzopyran-9-yl]oxy]-2-oxoethyl]thio]ethyl]-omega-methoxy	Mus musculus
PX-866	i.e. acetic acid 4-diallylaminomethylene-6-hydroxy-1-alpha-methoxymethyl-10beta,13beta-dimethyl-3,7,17-trioxo-1,3,4,7,10,11beta,12,13,14alpha,15,16,17-dodecahydro-2-oxacyclopenta[a]phenanthren-11-yl ester	Homo sapiens
PX-866	i.e. acetic acid 4-diallylaminomethylene-6-hydroxy-1-alpha-methoxymethyl-10beta,13beta-dimethyl-3,7,17-trioxo-1,3,4,7,10,11beta,12,13,14alpha,15,16,17-dodecahydro-2-oxacyclopenta[a]phenanthren-11-yl ester	Mus musculus
Wortmannin	an irreversible inhibitor with pan-PI3K activity	Homo sapiens
Wortmannin	an irreversible inhibitor with pan-PI3K activity	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
microsome	-	Mus musculus	-	-
microsome	-	Homo sapiens	-	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Mus musculus	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
A-498 cell	-	Homo sapiens	-
HT-29 cell	-	Homo sapiens	-
liver	-	Mus musculus	-
liver	-	Homo sapiens	-
U-87MG cell	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
PI3K	-	Mus musculus
PI3K	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Mus musculus
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Mus musculus
7.4	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Mus musculus
ATP	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	hyperactivation of the PI3K/AKT/mTOR signaling pathway is common in cancer, and PI3K and mTOR act synergistically in promoting tumor growth, survival, and resistance to chemotherapy	Homo sapiens

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Release 2023.1 (January 2023)