BAY 1436032

製品コードS8530 バッチS853001

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₆H₃₀F₃N₃O₃
	分子量	489.53	CAS No.	1803274-65-8
Solubility (25°C)*	体外	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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	NCH551b patient-derived glioma cell lines
	濃度	500 nM and 2.5 µM
	反応時間	1 day
	実験の流れ	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.
動物実験	動物モデル	BalbC nude mice
	投薬量	15-150 mg/kg
	投与方法	by oral gavage

参考

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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