| Description |
Mutant IDH1-IN-6 is a potent, selective and orally active mutant isocitrate dehydrogenase (IDH) inhibitor with IC50s 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[1].
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| Related Catalog |
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| Target |
IC50: 6.27 nM (IDH1 R132H), 3.71 nM (IDH1 R132C), 36.9 nM (IDH2 R140Q), 11.5 nM (IDH2 R172K), 105 nM (IDH1 wild-type) and 884 nM (IDH2 wild-type)[1]
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| In Vitro |
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].
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| In Vivo |
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.
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| References |
[1]. Renato Alejandro BAUER, et al. 7-phenylethylamino-4h-pyrimido[4,5-d][1,3]oxazin-2-one compounds as mutant idh1 and idh2 inhibitors. WO2018111707A1.
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