| Name | BAY-1436032 |
| Description | BAY-1436032 is a novel, selective and orally available inhibitor of pan-mutant isocitrate dehydrogenase 1 (IDH1). |
| 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. |
| 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. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 120 mg/mL (245.13 mM), Sonication and heating are recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 4 mg/mL (8.17 mM), Sonication is recommended.
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| Keywords | IsocitrateDehydrogenase(IDH) | IsocitrateDehydrogenase | Isocitrate Dehydrogenase (IDH) | Isocitrate Dehydrogenase | Inhibitor | inhibit | IDH1 | IDH | BAY-1436032 | BAY1436032 | BAY 1436032 |
| Inhibitors Related | Disulfiram | Mycophenolate Mofetil | Rotenone | Ribavirin | 18β-Glycyrrhetinic acid | Benzyl alcohol | 2-Methylaminoethanol | Methotrexate disodium | Dimethyl malonate | Isomalt | D-Mannitol | Ethyl potassium malonate |
| Related Compound Libraries | Bioactive Compound Library | ReFRAME Related Library | Glutamine Metabolism Compound Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Inhibitor Library | Orally Active Compound Library | Bioactive Compounds Library Max | Fluorochemical Library | Anti-Liver Cancer Compound Library | Anti-Cancer Drug Library | Anti-Cancer Active Compound Library |
United States
