Ivosidenib

Research use only, not for human use.

A mutant-selective inhibitor of IDH1.

A mutant-selective inhibitor of IDH1 (isocitrate dehydrogenase type 1); represent a worthwhile avenue of exploration in the treatment of IDH1-mutated tumors.Blood Cancer Phase 3 Clinical(In Vitro):Ivosidenib (AG-120) (0-13 μM; 48 hours) inhibits several IDH1-R132 mutants with potency similar IC50 values: IDH1-R132H (IC50=12 nM); IDH1-R132C (IC50=13 nM); IDH1-R132G (IC50=8 nM); IDH1-R132L (IC50=13 nM); IDH1-R132S (IC50=12 nM), respectively.(In Vivo):AG-120 (gavage administration; 50 mg/kg and 150 mg/kg) declines tumor 2-HG concentration rapidly, with maximum inhibition (92.0% and 95.2% at the 50 mg/kg and 150 mg/kg doses, respectively) achieved at -12 h post dose.

Ivosidenib (AG-120) (0-13 μM; 48 hours) inhibits several IDH1-R132 mutants with potency similar IC50 values: IDH1-R132H (IC50=12 nM); IDH1-R132C (IC50=13 nM); IDH1-R132G (IC50=8 nM); IDH1-R132L (IC50=13 nM); IDH1-R132S (IC50=12 nM), respectively.

AG-120 (gavage administration; 50 mg/kg and 150 mg/kg) declines tumor 2-HG concentration rapidly, with maximum inhibition (92.0% and 95.2% at the 50 mg/kg and 150 mg/kg doses, respectively) achieved at -12 h post dose. Animal Model:Female nude BALB/c mice inoculated with HT1080 cells Dosage:50 mg/kg and 150 mg/kg Administration:Gavage administration; 50 mg/kg and 150 mg/kg Result:Showed robust tumor 2-HG reduction in mouse.

AG-120

Metabolic Enzyme/Protease

IDH

IDH1

Cancer

Blood cancer

1448347-49-6

582.9609

C28H22ClF3N6O3

>98% (HPLC)

DMSO: ≥ 39 mg/mL

C1CC(=O)N(C1C(=O)N(C2=CC(=CN=C2)F)C(C3=CC=CC=C3Cl)C(=O)NC4CC(C4)(F)F)C5=NC=CC(=C5)C#N

Glycinamide, 1-(4-cyano-2-pyridinyl)-5-oxo-L-prolyl-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-N2-(5-fluoro-3-pyridinyl)-, (2S)-

(-20℃)

With Ice Pack

≥ 2 years