[(4R,5S)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-4,5-dimethyl-1H-imidazol-1-yl][4-[3-(methylsulfonyl)propyl]-1-piperazinyl]methanone

Description

RG-7112 is an inhibitor of mouse double-minute 2 protein (MDM2; IC₅₀ = 0.018 μM), an E3 ubiquitin ligase that ubiquitinates the tumor suppressor p53 and also acts as a negative regulator of p53 transcriptional activity. 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. It inhibits proliferation in cancer cell lines expressing wild-type p53 (IC₅₀s = 0.18-2.2 μM) and cell lines expressing mutant p53 (IC₅₀s = 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. 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.

Uses

RG 7112 is MDM2 antagonist. It can be used in biological study of single mouse analysis on evaluation of alternative in vivo drug screening methodology.

target

MDM2