Mutant IDH1-IN-6 is a potent, selective and orally active mutant isocitrate dehydrogenase (IDH) inhibitor with IC 50 s of 6.27 nM, 3.71 nM, 36.9 nM and 11.5 nM for IDH1 R132H , IDH1 R132C , IDH2 R140Q and IDH2 R172K mutant enzymes , respectively. Mutant IDH1-IN-6 is less active at inhibiting the IDH wild-type enzymes.

Mutant IDH1-IN-6 (example 2) inhibits production of 2-hydroxyglutarate in HT1080 cells with an IC50 of 1.28 nM, indicating the inhibition of mutant IDHl R132C in cells. aKG, a metabolite generated by wild-type IDHl is not affected by Mutant IDH1-IN-6, indicating Mutant IDH1-IN-6 is selective for mutant IDHl over wild type IDHl in cells[1].

Mutant IDH1-IN-6 (Example 2; 0-32 mg/kg; oral gavage; twice daily; for 3 days) treatment inhibitis of 2-hydroxyglutarate in a dose-dependent manner in IDHl mutant xenograft mice[1]. Animal Model: Athymic nude mice (20-22 g) injected with TB08 cells[1]Dosage: 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 16 mg/kg, 32 mg/kg Administration: Oral gavage; twice daily; for 3 days Result: Inhibitied of 2-hydroxyglutarate in IDHl mutant xenograft mice.

2230263-60-0

C28H36N6O3

504.635

Mutant IDH1-IN-6;Mutant IDH1-IN-6

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years