SP 141

SP-141 is a specific inhibitor of MDM2. SP-141 promotes MDM2 auto-ubiquitination and degradation. SP-141 might be used for the research of pancreatic cancer and breast cancer cells[1].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> MDM-2/p53

MDM2[1]

SP-141 (0.01-10 μM; 72 hours) inhibits human pancreatic cancer cell growth with IC50 values of less than 0.5 μM (0.38-0.50 μM) in a p53-independent manner. The IMR90 cells are much less sensitive to SP141 than the pancreatic cancer cells, suggesting that SP141 has a selective cytotoxicity for cancer cells[1]. SP141 induces MDM2 auto-ubiquitination and proteasomal degradation in both HPAC and Panc-1 cells[1]. Cell Viability Assay[1] 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[1] 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).

SP-141 (40 mg/kg; administered by i.p. injection; 5 d/wk for about three weeks) suppresses pancreatic tumor growth in both xenograft and orthotopic mouse models[1]. Animal Model: Nude mice bearing Panc-1 xenograft tumors[1] 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.

[1]. Wei Wang , et al. Identification of a New Class of MDM2 Inhibitor That Inhibits Growth of Orthotopic Pancreatic Tumors in Mice. Gastroenterology. 2014 Oct;147(4):893-902.e2.

[2]. Wei Wang, et al. The Pyrido[b]indole MDM2 Inhibitor SP-141 Exerts Potent Therapeutic Effects in Breast Cancer Models. Nat Commun. 2014 Oct 1;5:5086.