DS-3032b

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

DS-3032b 是一种有效的、选择性的、口服的 MDM2-p53 抑制剂，具有潜在的抗肿瘤活性。

DS-3032b is a potent, selective, orally available MDM2-p53 inhibitor with potential antineoplastic activity; binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53; restores p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis.Blood Cancer Phase 1 Clinical.

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).

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:50mg/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.

DS 3032b | DS3032b | Milademetan | DS 3032

Apoptosis

MDM2-p53

MDM2-p53

Cancer

Blood cancer

1398568-47-2

618.531

C30H34Cl2FN5O4

>98% (HPLC)

In Vitro:?DMSO : 16.67 mg/mL (26.95 mM)

CC1(CCC2(CC1)C3(C(C(N2)C(=O)NC4CCC(OC4)C(=O)N)C5=C(C(=NC=C5)Cl)F)C6=C(C=C(C=C6)Cl)NC3=O)C

(3'R,4'S,5'R)-N-((3S,6R)-6-carbamoyltetrahydro-2H-pyran-3-yl)-6''-chloro-4'-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indoline]-5'-carboxamide

(-20℃)

With Ice Pack

≥ 2 years