BAY-1436032
- Optical Purity: 99% e.e.
- Soluble in DMSO
- MF: C26H30F3N3O3
- MW: 489.53
Description
BAY-1436032 is a highly selective, potent and orally available inhibitor of mutant Isocitrate Dehydrogenase 1 (mIDH1). Optically pure BAY-1436032 is a double-digit nanomolar and selective pan-inhibitor of the enzymatic activity of various IDH1-R132X mutants in vitro and displayed potent inhibition of “oncometabolite” 2-hydroxyglutarate (2-HG) release (nM range) in patient derived and engineered cell lines expressing different IDH1 mutants. In line with the proposed mode of action, a concentration-dependent lowering of 2HG was observed in vitro accompanied by differentiation of maturation of mIDH1 tumor cells. It also showed a favorable selective profile against wIDH1/2 and a large panel of off-target proteins. Demonstrated a single agent in vivo efficacy in mIDH1 patient derived glioma and intrahepatic cholangiocarcinoma solid tumor model. It is highly effective against human IDH1 mutant acute myeloid leukemia in vivo. BBB penetrant.
More Information
| Parent CAS No. | 1803274-65-8 |
|---|---|
| Chemical Name | 3-(2-(4-(Trifluoromethoxy)phenylamino)-1-((1R,5R)-3,3,5-trimethylcyclohexyl)-1H-benzo[d]imidazol-5-yl)propanoic acid |
| extra_info | Sold in collaboration with Chemietek |
| SMILES | C1C2N=C(NC3C=CC(OC(F)(F)F)=CC=3)N([C@H]3CC(C)(C)C[C@@H](C)C3)C=2C=CC=1CCC(=O)O |&1:17,23,r| |
| MFCD | N.A. |
| InChi | InChI=1S/C26H30F3N3O3/c1-16-12-19(15-25(2,3)14-16)32-22-10-4-17(5-11-23(33)34)13-21(22)31-24(32)30-18-6-8-20(9-7-18)35-26(27,28)29/h4,6-10,13,16,19H,5,11-12,14-15H2,1-3H3,(H,30,31)(H,33,34)/t16-,19+/m0/s1 |
| InChiKey | RNMAUIMMNAHKQR-QFBILLFUSA-N |
| CID | 118310260 |
| Short Description | Mutant Isocitrate Dehydrogenase 1 (mIDH1) inhibitor |
References
- A Chaturvedi et al. Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo. Leukemia. 2017 Oct;31(10):2020-2028.
- M Heuser et al. Pan-Mutant-IDH1 Inhibitor Bay-1436032 Is Highly Effective Against Human IDH1 Mutant Acute Myeloid Leukemia In Vivo. Blood 2016 128:745.
