APG-1387, a bivalent SMAC mimetic and an IAP antagonist, blocks the activity of IAPs family proteins (XIAP, cIAP-1 , cIAP-2 , and ML-IAP). APG-1387 induces degradation of cIAP-1 and XIAP proteins, as well as caspase-3 activation and PARP cleavage, which leads to apoptosis . APG-1387 can be used for the research of hepatocellular carcinoma, ovarian cancer , and nasopharyngeal carcinoma
In Vitro
APG-1387 (0.02-20 μM; 24 h) induces rapid degradation of cIAPs in HepG2 and HCCLM3 cells. APG-1387 (2 μM; 24 h) enhances TNF-α- and TRAIL-mediated anti-cancer activities in HepG2 and HCCLM3 cells. APG-1387 sensitizes HepG2 and HCCLM3 cells to NK cell-mediated killing in vitro. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: HepG2 and HCCLM3 cells Concentration: 0.02, 0.2, 2, 20 μM Incubation Time: 1, 6, 24 hours Result: Decreased the expression of cIAP1 and cIAP2 in both cell lines in a dose- and time-dependent manner. Inhibited the expression of X chromosome-linked IAP (XIAP) at a high dose.
In Vivo
APG-1387 (20 mg/kg; i.p. every 3 days for 4 weeks) sensitizes HCCLM3 tumors toward NK cell-mediated killing in mice . APG-1387 (20 mg/kg; i.p. every 3 days for 4 weeks) monotherapy exhibits some degree of anti-tumor effect and is well tolerated in mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Non-obese diabetic and severe combined immunodeficiency (NOD-SCID) mice bearing HCCLM3 tumors are injected with NK cells Dosage: 20 mg/kg Administration: I.p. every 3 days for 4 weeks Result: Decreased the expression of cIAP1 and cIAP2, and less potent to XIAP expression. Potentiated the effects of pre-activated NK cells on HCCLM3 xenograft tumor growth and tumor weight.
