AMG 232 is a highly potent, selective and orally bioavailable piperidinone inhibitor of the MDM2-p53 interaction((SPR KD= 0.045 nM, SJSA-1 EdU IC50=9.1 nM).

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

AMG-232, AMG 232

10 mM in DMSO

MDM-2_p53

AMG 232 (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN). AMG 232 significantly inhibits the human MDM2-p53 interaction in the biochemical HTRF-based assay (IC50=0.6 nM). AMG 232 potently inhibits proliferation of non-MDM2-amplified HCT116 colorectal cells in the BrdU assay (IC50=10 nM).

AMG 232 (10, 25, 75 mg/kg, p.o.) activates p53 pathway activity in vivo. AMG 232 (100 mg/kg, p.o.) results in 86% TGI compared with control, and the ED50 is 31 mg/kg in the HCT116 colorectal cancer model (KRAS mutant), and results in 97% TGI, with an ED50 of 18 mg/kg in an A375sq2 BRAF-mutant melanoma model. AMG 232 exhibits low clearance (42%), but high clearance (0.74 × Qh) and low oral exposure in dogs (18%). AMG 232 displays robust tumor growth inhibition compared to the vehicle, with an ED50 of 9.1 mg/kg q.d. AMG 232 causes a dose-dependent tumor growth inhibition with an ED50 of 16 mg/kg.