同义名 :	-
	CAS号 :	1628805-46-8
	货号 :	A943584
	分子式 :	C23H22F4N6O2
	纯度 :	98%
	分子量 :	490.45
	MDL号 :	MFCD31630851
	存储条件：	Pure form Inert atmosphere, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性
描述	Isocitrate dehydrogenase 1 (IDH1) is a NADP+ , metal dependent oxidoreductase and wild-type IDH1 catalyzes the oxidative decarboxylation of isocitrate to give α-ketoglutarate (α-KG), while NADP+ is converted to NADPH. Mutations in IDH1 at Arg132 have been tightly associated to various cancers, including glioma, glioblastoma, AML, chondrosarcoma, and cholangiocarcinoma[2]. IDH-305 is a potent and selective inhibitor of IDH1 R132H and R132C with IC50 of 27 and 28 nM, respectively. HCT116-IDH1R132H+/- mechanistic xenograft model treated with a single oral dose of 200 mg/kg IDH-305 showed reduction of tumor 2-HG concentration with maximal 2-HG inhibition of 87.2 ± 1.5% relative to the vehicle treated tumors 8 h post treatment[2].
作用机制	IDH-305 demonstrated a hydrophobic collapse conformation. The aminopyrimidine moiety forms a pair of hydrogen bonds with the backbone atoms of Ile128, while the carbonyl of the oxazolidinone forms a hydrogen bond with the backbone amide of Leu120, and the alpha-methyl fits into the methyl nook.

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.04mL 0.41mL 0.20mL	10.19mL 2.04mL 1.02mL	20.39mL 4.08mL 2.04mL

参考文献

[1]Cho YS, Levell JR, et al. Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor. ACS Med Chem Lett. 2017 Sep 18;8(10):1116-1121. [2]Cho YS, Levell JR, Liu G, Caferro T, Sutton J, Shafer CM, Costales A, Manning JR, Zhao Q, Sendzik M, Shultz M, Chenail G, Dooley J, Villalba B, Farsidjani A, Chen J, Kulathila R, Xie X, Dodd S, Gould T, Liang G, Heimbach T, Slocum K, Firestone B, Pu M, Pagliarini R, Growney JD. Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor. ACS Med Chem Lett. 2017 Sep 18;8(10):1116-1121. doi: 10.1021/acsmedchemlett.7b00342. PMID: 29057061; PMCID: PMC5641959.