RG-7112 is an inhibitor of mouse double-minute 2 protein (MDM2; IC
50 = 0.018 μM), an E3 ubiquitin ligase that ubiquitinates the tumor suppressor p53 and also acts as a negative regulator of p53 transcriptional activity.
1 RG-7112 binds to the p53 binding pocket of MDM2. It increases the levels of p53 and its transcriptional targets in SJSA-1 osteosarcoma cells.
1,2 It inhibits proliferation in cancer cell lines expressing wild-type p53 (IC
50s = 0.18-2.2 μM) and cell lines expressing mutant p53 (IC
50s = 5.7-20.3 μM). RG-7112 also prevents and reduces tumor growth in an SJSA-1 mouse xenograft model when administered at doses of 50 and 100 mg/kg per day, respectively.
2 However, it inhibits thrombopoiesis
in vivo, decreasing platelet counts in rats when administered at doses of 50 and 100 mg/kg and in cynomolgus monkeys at doses of 10 and 20 mg/kg.
3 
