SP 141

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

SP 141是一种MDM2抑制剂。SP-141促进MDM2自动泛素化和降解，具有抗癌活性。SP141直接与MDM2结合，促进其被蛋白酶体自动泛素化和降解。

SP 141 is a MDM2 inhibitor.SP-141 promotes MDM2 auto-ubiquitination and degradation, with anticancer activity.SP141, which bound directly to MDM2, promoting its auto-ubiquitination and degradation by the proteasome.?The compound reduced levels of MDM2 in pancreatic cancer cell lines, as well as their proliferation, with 50% inhibitory concentrations <0.5 μM (0.38-0.50 μM).?Increasing concentrations of SP141 induced increasing levels of apoptosis and G2-M-phase arrest of pancreatic cancer cell lines, whether or not they expressed functional P53.?Injection of nude mice with SP141 (40 mg/kg/d) inhibited growth of xenograft tumors (by 75% compared with control mice), and led to regression of orthotopic tumors.

Cell Viability Assay Cell Line:HPAC, Panc-1, AsPC-1, and Mia-Paca-2 pancreatic cancer cell lines. Human primary fibroblasts (IMR90)Concentration:0.01, 0.1, 1, and 10 μM Incubation Time:72 hours Result:IC50s of 0.38, 0.50, 0.36, 0.41, and 13.22 μM for HPAC, Panc-1, AsPC-1, Mia-Paca-2, and IMR90, respectively.Western Blot Analysis Cell Line:HPAC and Panc-1 cells Concentration:0.5 μM Incubation Time:120 minutes Result:Reduced the MDM2 protein levels.Increased the degradation rate of the MDM2 protein in the presence of Cycloheximide (15 μg/mL).

Animal Model:Nude mice bearing Panc-1 xenograft tumors Dosage:40 mg/kg Administration:Administered by i.p. injection; 5 d/wk for about three weeks Result:Significantly suppressed the growth of pancreatic xenograft tumors. On Day 18, the tumor volume in the treated group was reduced by 75% compared with that in the control group. There were no significant differences in the body weight compared with the control group.

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Apoptosis

MDM2-p53

Mdm2

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1253491-42-7

324.38

C22H16N2O

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (385.35 mM)

COc1ccc2[nH]c3c(nccc3c2c1)-c1cccc2ccccc12

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(-20℃)

With Ice Pack

≥ 2 years