In vitro: BAY1436032 inhibited intracellular R-2HG production in mouse hematopoietic cells expressing IDH1R132H or IDH1R132C with an IC50 of 60 and 45 nm, respectively. In contrast, R-2HG levels were not reduced in IDH2R140Q and IDH2R172K expressing mouse hematopoietic cells by BAY1436032 at concentrations up to 10 μm.
In vivo: Treatment with vehicle or 150 mg/kg BAY1436032 once daily by oral gavage was initiated at day 15 after transplantation. BAY1436032 and vehicle-treated mice had similar percentages of hCD45+ cells, peripheral blood counts, spleen weight at death and survival, confirming the on-target activity of BAY1436032
|Cell lines||HoxA9-IDH1R132 cell lines|
|Preparation method||Vehicle or BAY1436032 was added to methylcellulose containing 105 human mononuclear cells, which were plated in duplicate. Colonies were evaluated microscopically 10 to 14 days after plating by standard criteria.|
|Incubation time||24 h|
|Animal models||NSG mice|
|Dosages||45 or 150 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo.
Chaturvedi A, et al. Leukemia. 2017 Oct;31(10):2020-2028. PMID: 28232670.
Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo.
Pusch S, et al. Acta Neuropathol. 2017 Apr;133(4):629-644. PMID: 28124097.
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