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.
IC50&Target
MDM2.
体外研究
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.
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).
体内研究
Milademetan (DS-3032b, 50 mg/kg, oral gavage) delays tumor growth and improves survival in mice xenografted with neuroblastoma cells with functional TP53.
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.
分子量
618.53
CAS号
1398568-47-2
运输条件
Room temperature in continental US; may vary elsewhere.