Alrizomadlin

Alrizomadlin (APG-115) is an orally active MDM2 protein inhibitor binding to MDM2 protein with IC₅₀ and K_i values of 3.8 nM and 1 nM, respectively^[1]. Alrizomadlin blocks the interaction of MDM2 and p53 and induces cell-cycle arrest and apoptosis in a p53-dependent manner^[2][3]. IC50 & Target: IC50: 3.8 nm (APG-115)^[1] In Vitro: Alrizomadlin (0.001-100 μM; 72 hours) inhibits cell proliferation in concentration-dependent manner, with IC₅₀s of 18.9 ± 15.6 nM and 103.5 ± 18.3 nM respectively in AGS and MKN45 cells^[3].
Alrizomadlin (0.02 μM, 0.2 μM; 48 hours) enhances the anti-proliferative effect of radiotherapy at different radiation dose^[3].
Alrizomadlin (0.02 μM, 0.2 μM; 48 hours) affects progression by inducing cells arrested at G0/G1 phase in AGS and MKN45 cell with wild p53^[3].
Alrizomadlin (0.02 μM, 0.2 μM; 24 hours) activates p53 to enhance radiosensitivity in AGS and MKN45 cells; stable knockout of p53 abrogates expression of MDM2, p53, p21, PUMA, BAX, Cleaved-caspase3, γH2AX^[3].
Alrizomadlin (0.3 μM, 1 μM, 3 μM, 10 μM; 24 hours) leads to a concentration-dependent cell cycle arrest in G2/M phases and a decreasing in S-phase in p53 wide-type cell lines (TPC-1, KTC-1)^[4]. In Vivo: Alrizomadlin (Delivered orally; 100 mg/kg; once daily; 10 days) enhances radiation antitumor effect in gastric adenocarcinoma in vivo^[3].