Milademetan (DS-3032) is a specific and orally active MDM2 inhibitor for the research of acute myeloid leukemia (AML) or solid tumors. Milademetan (DS-3032) induces G1 cell cycle arrest , senescence and apoptosis
In Vitro
Milademetan (DS-3032) can stabilize TP53 and selectively induce CDKNA1, BAX and MDM2 expression in neuroblastoma cells with wild-type TP53. Milademetan (DS-3032b) treatment enhances TP53 target gene expression and induces G1 cell cycle arrest , senescence and apoptosis. Milademetan (DS-3032b, 0-2000 nM) treatment selectively inhibits viability, proliferation and migration of neuroblastoma cells with wildtype TP53 independently of MYCN status . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability Assay Cell Line: SK-N-SH, SH-SY5Y, IMR32, IMR5 and LAN5 cell lines. Concentration: 0-2000 nM. Incubation Time: 24-72 h. Result: Reduced viability in a dose- and time-dependent manner. Exhibited IC50 values of 21.9 nM, 17.7 nM, 52.63 nM, 25.7 nM and 44.1 nM in SK-N-SH, SH-SY5Y, IMR32, IMR5 and LAN5 cell lines, respectively (72 h).
In Vivo
Milademetan (DS-3032b, 50 mg/kg, oral gavage) delays tumor growth and improves survival in mice xenografted with neuroblastoma cells with functional TP53. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: SH-SY5Y xenograft tumors in nude mice. Dosage: 50 mg/kg. Administration: Oral gavage for 30 consecutive days with an alternating schedule of 4 days of daily treatment with oral gavages followed by 2 days without treatment (4+2). Result: Survival in the mouse cohort was significantly prolonged. Reduced neuroblastoma xenograft tumor growth by activating TP53 signaling.
Form:Solid
IC50& Target:MDM2
