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AGI-6780

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Chemical Structure| 1432660-47-3 同义名 : -
CAS号 : 1432660-47-3
货号 : A254962
分子式 : C21H18F3N3O3S2
纯度 : 99%+
分子量 : 481.511
MDL号 : MFCD26097285
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(62.3 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Dehydrogenase

    IDH2 R140Q mutant, IC50:23 nM
描述 Isocitrate dehydrogenase is a metabolic enzyme that interconverts isocitrate and alpha-ketoglutarate. The somatic point mutations in IDH1 and IDH2 alter the residues in the enzyme active sites, thereby inducing tumorigenesis. AGI-6780 is a small molecule inhibitor that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q with an IC50 value of 23nM. AGI-6780 also inhibited the formation of oncometabolite (R)-2-hydroxyglutarate (2HG) in TF-1 (IDH2-R140Q) and U87 (IDH2-R140Q) cell lines with IC50 values of 18nM and 11nM, respectively. Pretreatment of AGI-6780 at the doses of 0.2 and 11μM restored the mRNA expression of hemoglobin G1/2 and KLF1 in TF1/R140Q cells in the presence of erythropoietin. In primary patient samples of IDH2/R140Q acute myelogenous leukemia, treatment of 0.5-5μM AGI-6780 dose-dependently decreased the amounts of extracellular and intracellular 2HG. AGI-6780 treatment also increased the number of CD11b-, CD14-, CD15-, and MPO-positive cells in IDH2/R140Q patient samples, but not in IDH2/WT samples. In the presence of 5μM AGI- 6780, unfractionated nucleated bone marrow cells showed a threefold increase in the number of colony- forming units as compared to vehicle-treated cells[3].
作用机制 AGI-6780 inhibits IDH2/R140Q via binding at the dimer interface in an allosteric manner[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.08mL

0.42mL

0.21mL

10.38mL

2.08mL

1.04mL

20.77mL

4.15mL

2.08mL
参考文献

[1]Kernytsky A, Wang F, et al. IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition. Blood. 2015 Jan 8;125(2):296-303.

[2]Wang F, Travins J, et al. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013 May 3;340(6132):622-6.

[3]Wang F, Travins J, DeLaBarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C, Yang H, Gross S, Artin E, Saada V, Mylonas E, Quivoron C, Popovici-Muller J, Saunders JO, Salituro FG, Yan S, Murray S, Wei W, Gao Y, Dang L, Dorsch M, Agresta S, Schenkein DP, Biller SA, Su SM, de Botton S, Yen KE. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013 May 3;340(6132):622-6.