BAY 1436032

Catalog No.S8530 Batch:S853001

Technical Data

Formula	C₂₆H₃₀F₃N₃O₃
Molecular Weight	489.53	CAS No.	1803274-65-8
Solubility (25°C)*	In vitro	DMSO	98 mg/mL (200.19 mM)
		Ethanol	98 mg/mL (200.19 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

BAY-1436032 is a highly selective, potent and orally available inhibitor of mutant Isocitrate Dehydrogenase 1 (mIDH1). It is a double-digit nanomolar and selective pan-inhibitor of the enzymatic activity of various IDH1-R132X mutants in vitro and displays potent inhibition of 2-HG release (nanomolar range) in patient derived and engineered cell lines expressing different IDH1 mutants.

Targets

IDH1 (R132H) ^[1] (Cell-free assay)	IDH1 (R132C) ^[1] (Cell-free assay)
15 nM	15 nM

In vitro

BAY 1436032 exhibits an IC50 of 15 nM for mutant IDH1R132H protein and virtually no effect on wild-type IDH1 and the structurally related IDH2 proteins with IC50 of 20 and >100 µM, respectively. BAY 1436032 not only reduces 2-HG levels in cells with the IDH1R132H or the IDH1R132C mutations, but also in those with the R132G, R132S or R132L mutations with equal efficiency. There is no inhibition of IDH2 R172M. BAY 1436032 reduces proliferation and induces differentiation in primary glioma cultures. BAY 1436032 reveals low metabolic clearance (CL) in vitro in rat hepatocytes and mice liver microsomes^[1].

In vivo

The pharmacokinetic properties of BAY 1436032 allow for oral administration. In vivo pharmacokinetics (PK) in rats shows low CL and high oral bioavailability. Oral administration of BAY 1436032 confers a survival benefit to mice transplanted with IDH1 mutant tumors. BAY 1436032 induces differentiation in intracranial xenografts^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines NCH551b patient-derived glioma cell lines Concentrations 500 nM and 2.5 µM Incubation Time 1 day Method Cells are seeded with 4000 cells/well in 96-well plates for suspension cells. For each condition, three wells are used. The cells are treated 1 day after seeding with BAY 1436032 at concentrations of 500 nM and 2.5 µM and DMSO as solvent control. Subsequently, measurements are performed on days 7, 14 and 21 after the first inhibitor treatment. The cells receive fresh drug-containing medium after the first 7 and 14 days of treatment. Plates are measured with a microplate reader.
Animal Study:^{^[1]}	Animal Models BalbC nude mice Dosages 15-150 mg/kg Administration by oral gavage

Cell Assay:^{^[1]}

Cell lines
NCH551b patient-derived glioma cell lines
Concentrations
500 nM and 2.5 µM
Incubation Time
1 day
Method
Cells are seeded with 4000 cells/well in 96-well plates for suspension cells. For each condition, three wells are used. The cells are treated 1 day after seeding with BAY 1436032 at concentrations of 500 nM and 2.5 µM and DMSO as solvent control. Subsequently, measurements are performed on days 7, 14 and 21 after the first inhibitor treatment. The cells receive fresh drug-containing medium after the first 7 and 14 days of treatment. Plates are measured with a microplate reader.

Animal Study:^{^[1]}

Animal Models
BalbC nude mice
Dosages
15-150 mg/kg
Administration
by oral gavage

References

[1] Pusch S, et al. Acta Neuropathol. 2017, 133(4):629-644.

Selleck's BAY 1436032 has been cited by 2 publications

Treatment strategy for hepatocellular carcinoma based on metabolism [ Yonsei University Medical Library, 2022, ]	PubMed: none
Synergistic activity of IDH1 inhibitor BAY1436032 with azacitidine in IDH1 mutant acute myeloid leukemia. [ Haematologica, 2020, 2 pii: haematol]	PubMed: 32241846

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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