MD-224

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

MD-224 是一种基于蛋白水解靶向嵌合体 (PROTAC) 概念的高效 MDM2 降解剂，是一类新型抗癌剂。

MD-224 is a highly potent and efficacious MDM2 degrader based on the proteolysistargeting chimera (PROTAC) concept，and as a new class of anticancer agent.MD-224 effectively induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells.?It achieves an IC50 value of 1.5 nM in inhibition of growth of RS4;11 cells and also low nanomolar IC50 values in a panel of leukemia cell lines.?MD-224 achieves complete and durable tumor regression in vivo in the RS4;11 xenograft tumor model in mice at well-tolerated dose schedules.

MD-224 (1-30 nM; 2 hours) effectively induces depletion of MDM2 protein and concurrently accumulation of p53 protein in a dose-dependent manner in RS4;11 cells.?MD-224 (30 nM; 6 hours) is more potent than MI-1061 in induction of transcriptional upregulation of these p53 target genes but have no effect on TP53 itself in RS4;11 cells.MD-224 (0.001-1 μM; 24 hours) induces robust apoptosis at ≤10 nM in a dose-dependent manner upon a 24 hours treatment.Western Blot Analysis Cell Line:RS4;11 cells Concentration:1 nM; 3 nM; 10 nM; 30 nM Incubation Time:2 hoursResult:Decreased MDM2 protein and accumulated of p53 protein.RT-PCRCell Line:RS4;11 cells Concentration:30 nM Incubation Time:6 hours Result:Upregulated p53 target gene expression.Apoptosis Analysis Cell Line:RS4;11 cells Concentration:0.001 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM Incubation Time:24 hours Result:Induces robust apoptosis in RS4;11 cells.

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Apoptosis

MDM2-p53

Mdm2|PROTAC

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2136247-12-4

889.8

C48H43Cl2FN6O6

>98% (HPLC)

DMSO:150 mg/mL (168.58 mM; Need ultrasonic)

Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCC#Cc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O

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(-20℃)

With Ice Pack

≥ 2 years