BAY-1436032 |
Catalog No.GC19059 |
BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1803274-65-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | 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]. |
Animal experiment: | 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]. |
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. |
BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor.
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 uM. Colony growth is inhibited by 50% at a concentration of 0.1 uM BAY-1436032, while concentrations up to 100 uM 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].
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].
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.
Cas No. | 1803274-65-8 | SDF | |
Canonical SMILES | O=C(O)CCC1=CC=C2C(N=C(NC3=CC=C(OC(F)(F)F)C=C3)N2[C@H]4CC(C)(C)C[C@@H](C)C4)=C1 | ||
Formula | C26H30F3N3O3 | M.Wt | 489.53 |
Solubility | DMSO : 125 mg/mL (255.35 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.0428 mL | 10.2139 mL | 20.4278 mL |
5 mM | 0.4086 mL | 2.0428 mL | 4.0856 mL |
10 mM | 0.2043 mL | 1.0214 mL | 2.0428 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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