EC Number   |
Inhibitors |
Structure |
|---|
    1.1.1.42 | (+)-ML309 |
reversible binding analysis and mechanism, detailed overview. The reversible inhibitor binds to IDH1 R132H competitively with respect to 2-oxoglutarate and uncompetitively with respect to NADPH. ML309 competes with 2-oxoglutarate but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-hydroxyglutarate levels. The rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active, whereas the (-) isomer is over 400fold less active for IDH1 R132H inhibition. IDH1 R132C is similarly inhibited by (-)-ML309. ML309 is also able to inhibit 2-hydroxyglutarate production in a glioblastoma cell line and had minimal cytotoxicity. In the presence of racemic ML309, 2-hydroxyglutarate levels drop rapidly |
   |
| 1.1.1.42 | (-)-ML309 |
reversible binding analysis and mechanism, detailed overview. The reversible inhibitor binds to IDH1 R132H competitively with respect to 2-oxoglutarate and uncompetitively with respect to NADPH. ML309 competes with 2-oxoglutarate but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-hydroxyglutarate levels. The rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active, whereas the (-) isomer is over 400fold less active for IDH1 R132H inhibition. IDH1 R132C is similarly inhibited by (-)-ML309. Wild-type IDH1 is largely unaffected by (+)-ML309. ML309 is also able to inhibit 2-hydroxyglutarate production in a glioblastoma cell line and had minimal cytotoxicity. In the presence of racemic ML309, 2-hydroxyglutarate levels drop rapidly |
|
| 1.1.1.42 | (5aS,6S,9aR)-2-benzoyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile |
- |
|
| 1.1.1.42 | (5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile |
- |
|
| 1.1.1.42 | (6aS,7S,10aR)-2-anilino-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile |
- |
|
| 1.1.1.42 | (6aS,7S,10aR)-7,10a-dimethyl-8-oxo-2-(phenylamino)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile |
- |
|
| 1.1.1.42 | (6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-[(pyridin-3-yl)amino]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile |
- |
|
| 1.1.1.42 | (6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile |
- |
|
| 1.1.1.42 | (6aS,7S,10aS)-2-anilino-7-methyl-10a-phenyl-5,6a,7,10a-tetrahydrobenzo[h]quinazolin-8(6H)-one |
- |
|
| 1.1.1.42 | (7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1R)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide |
- |
|
