tcsc2686 MI-773

MI-773 is a new small molecule inhibitor of the MDM2-p53 interaction, binds to MDM2 with high affinity (K_i=0.88 nM) and blocks the p53-MDM2 interaction.

IC50 & Target: Ki: 0.88 nM (MDM2)^[1]

In Vitro: MI-773 potently induces expression of p53 and its downstream targets p21, MDM2, and induces phosphorylation of p53 (serine 392) in low passage primary human ACC cells. Notably, MI-773 induces a dose-dependent increase in the fraction of apoptotic ACC cells and in the fraction of cells in the G1 phase of cell cycle (P<0.05). Consequently, MI-773 causes apoptotic cell death^[1]. MI-773 is an advanced synthetic small molecule inhibitor, displays high binding affinity against MDM2 (K_d=8.2 nM)^[2].

In Vivo: MI-773 at 10 mg/kg modestly reduces the rate of tumor growth, whereas 100 mg/kg causes significant tumor regression. Control tumors reach an average of 1,000 mm³ at 20 days of treatment, compare to an average volume of 600 mm³ for the 10 mg/kg group and 30 mm³ for the 100 mg/kg group. Kaplan-Meier analysis shows an increase in tumor failure, define as two times increase in tumor volume as compared to pretreatment volume (P=0.044), for vehicle-treated mice when compare to mice treated with 100 mg/kg MI-773^[1].