Introduction：Basic information about CAS 1803274-65-8|BAY-1436032, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | BAY-1436032 |
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| CAS Number | 1803274-65-8 | Molecular Weight | 489.53 |
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| Density | / | Boiling Point | / |
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| Molecular Formula | C26H30F3N3O3 | Melting Point | / |
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| MSDS | / | Flash Point | / |
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Names
| Name | 2-[[4-(Trifluoromethoxy)phenyl]amino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazole-5-propanoic acid |
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| Synonym | More Synonyms |
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BAY-1436032 BiologicalActivity
| Description | BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor. |
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| Related Catalog | Signaling Pathways >>Metabolic Enzyme/Protease >>Isocitrate Dehydrogenase (IDH)Research Areas >>Cancer |
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| Target | IDH1[1] |
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| In Vitro | BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor. BAY-1436032 inhibits intracellular (R)-2-hydroxyglutarate (R-2HG) production in mouse hematopoietic cells expressing IDH1R132H or IDH1R132C with IC50s of 60 and 45 nM, respectively. R-2HG levels are not reduced in IDH2R140Q and IDH2R172K expressing mouse hematopoietic cells by BAY-1436032 at concentrations up to 10 μM. Colony growth is inhibited by 50% at a concentration of 0.1 μM BAY-1436032, while concentrations up to 100 μM do not suppress colony growth of patient-derived IDH1 wild-type AML cells. On morphologic evaluation myelomonocytic differentiation of myeloid progenitors is strongly induced by BAY-1436032[1]. |
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| In Vivo | Long-term exposure to once daily oral BAY-1436032 reveals nearly complete suppression of (R)-2-hydroxyglutarate (R-2HG) production with 150 mg/kg BAY1436032. White blood cell counts constantly increase in vehicle-treated mice and, at a lower rate, in animals receiving 45 mg/kg BAY-1436032, while they remain constant in the 150 mg/kg cohort. Hemoglobin levels are slightly lower in the vehicle and 45 mg/kg groups as compare to the 150 mg/kg cohort at day 60, while platelet counts are significantly reduced in vehicle and 45 mg/kg BAY-1436032 treated mice compare to the 150 mg/kg cohort at day 60. All mice receiving 150 mg/kg BAY-1436032 survive with minimal hCD45+ cell load in their peripheral blood until the end of observation at day 150 after treatment start (P<0.001), while vehicle-treated animals die from leukemia with a median survival of 91 days. Mice treated with 45 mg/kg BAY-1436032 display intermediate levels of CD14/CD15 expression[1]. |
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| Cell Assay | Colony-forming cell (CFC) units are assayed in methylcellulose supplemented with 10 ng/mL IL-3, 10 ng/mL GM-CSF, 50 ng/ mL SCF, 50 ng/mL FLT3-ligand and 3 U/mL EPO. Vehicle or BAY-1436032 is added to methylcellulose containing 105 human mononuclear cells, which are plated in duplicate. Colonies are evaluated microscopically 10 to 14 days after plating by standard criteria[1]. |
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| Animal Admin | NSG mice are used and transplanted with primary acute myeloid leukemia (AML) cells from a patient with IDH1R132C mutant AML. Per condition 10 mice are treated with vehicle, 45 or 150 mg/kg body weight BAY-1436032 once daily by oral gavage for 150 days starting 17 days after transplantation. Finally, serum R-2HG levels and human CD45+ (hCD45+) cells are measured[1]. |
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| References | [1]. Chaturvedi A, 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. |
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Chemical & Physical Properties
| Molecular Formula | C26H30F3N3O3 |
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| Molecular Weight | 489.53 |
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| InChIKey | RNMAUIMMNAHKQR-QFBILLFUSA-N |
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| SMILES | CC1CC(n2c(Nc3ccc(OC(F)(F)F)cc3)nc3cc(CCC(=O)O)ccc32)CC(C)(C)C1 |
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| Storage condition | 2-8℃ |
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Synonyms
