| Product Description | Alrizomadlin (APG-115) is an orally active MDM2 protein inhibitor binding to MDM2 protein with IC 50 and K i values of 3.8 nM and 1 nM, respectively Alrizomadlin blocks the interaction of MDM2 and p53 and induces cell-cycle arrest and apoptosis in a p53-dependent manner In Vitro Alrizomadlin (0.001-100 μM; 72 hours) inhibits cell proliferation in concentration-dependent manner, with IC 50 s of 18.9?±?15.6 nM and 103.5?±?18.3 nM respectively in AGS and MKN45 cells. ?\nAlrizomadlin (0.02 μM, 0.2 μM; 48 hours) enhances the anti-proliferative effect of radiotherapy at different radiation dose. ?\nAlrizomadlin (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. ?\nAlrizomadlin (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. ?\nAlrizomadlin (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) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: AGS and MKN45 cells Concentration: 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM Incubation Time: 72 hours Result: Inhibited cell proliferation in a concentration-dependent manner. RT-PCRCell Line: AGS and MKN45 cells Concentration: 0.02 μM, 0.2 μM Incubation Time: 48 hours Result: Elevated MDM2, p21, PUMA and BAX mRNA expression. Cell Cycle AnalysisCell Line: AGS and MKN45 cells Concentration: 0.02 μM, 0.2 μM Incubation Time: 48 hours Result: Arrested cells at G0/G1 phase. Apoptosis Analysis Cell Line: DePTC p53 wide-type cell line: TPC-1 cells, KTC-1 cells Concentration: 0.3μM, 1μM, 3μM, 10 μM Incubation Time: 24 hours Result: Reduced cell population in S-phase, whereas accumulation of cells at G2/M phases. Western Blot AnalysisCell Line: AGS and MKN45 cells Concentration: 0.2 μM Incubation Time: 72 hours Result: Enhanced expressions of MDM2 and p53, stable knockout of p53 abrogated them. In Vivo Alrizomadlin (Delivered orally; 100 mg/kg; once daily; 10 days) enhances radiation antitumor effect in gastric adenocarcinoma in vivo. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Four-week-old male BALB/c athymic nude mice with MKN45 cellsDosage: 100 mg/kg Administration: Deliverer orally; once daily; 10 days Result: Decreased xenograft tumor growth. Form:Solid IC50& Target:IC50: 3.8 nm (APG-115) |
|---|
