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Catalog No. TQ0042   CAS 1803274-65-8

BAY-1436032 is a novel, selective and orally available inhibitor of pan-mutant isocitrate dehydrogenase 1 (IDH1).

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BAY-1436032, CAS 1803274-65-8
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Purity: 98%
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Biological Description
Chemical Properties
Storage & Solubility Information
Description BAY-1436032 is a novel, selective and orally available inhibitor of pan-mutant isocitrate dehydrogenase 1 (IDH1).
In vitro BAY-1436032 inhibits intracellular (R)-2-hydroxyglutarate (R-2HG) production in mouse hematopoietic cells expressing IDH1R132H or IDH1R132C (IC50s: 60 and 45?nM). 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.
In vivo Long-term exposure to once-daily oral BAY-1436032 reveals nearly complete suppression of 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 compared to the 150?mg/kg cohort at day 60, while platelet counts are significantly reduced in the vehicle and 45?mg/kg BAY-1436032 treated mice compared 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, 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.
Cell Research 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 1 × 10^5 human mononuclear cells, which are plated in duplicate. Colonies are evaluated microscopically 10 to 14 days after plating by standard criteria.
Animal Research 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.
Molecular Weight 489.53
Formula C26H30F3N3O3
CAS No. 1803274-65-8


Powder: -20°C for 3 years

In solvent: -80°C for 2 years

Solubility Information

DMSO: 120 mg/mL (245.14 mM), Need ultrasonic and warming

( < 1 mg/ml refers to the product slightly soluble or insoluble )

References and Literature

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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