tcsc0330 RG7112

RG7112 is the first clinical and orally available MDM-2/p53 inhibitor designed to occupy the p53-binding pocket of MDM2, with the K_d value of 11 nM.

IC50 & Target: Kd: 11 nM (MDM2)^[1]

In Vitro: RG7112 (2.5μM) is more active against proliferation of liposarcoma cells, and especially those with wild-type p53. Treatment of cells with either Nutlin-3A or RG7112 induces cell-cycle arrest and apoptosis in the p53-WT cell line 93T449. RG7112 treatment reduces cell viability much more than Nutlin-3A in HT-1080, SW684, 93T449, and SW872 cells^[1]. RG7112 shows potent antitumor activity against a panel of solid tumor cell lines. Treatment of cancer cells expressing wild-type p53 with RG7112 activates the p53 pathway, leading to cell-cycle arrest and apoptosis^[2].

In Vivo: RG7112 is highly synergistic with androgen deprivation in LNCaP xenograft tumors. RG7112 (25-200 mg/kg, p.o.) to human xenograft-bearing mice at nontoxic concentrations causes dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression^[2].