SP 141

Cas No.:	1253491-42-7
Chemical Name:	6-​methoxy-​1-​(1-​naphthalenyl)-​9H-​pyrido[3,​4-​b]indole
Synonyms:	SP 141，SP141，
SMILES:	COC1=CC2=C(NC3=C2C=CN=C3C4=C5C=CC=CC5=CC=C4)C=C1
Formula:	C22H16N2O
M.Wt:	324.38
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	[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.

Description:	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].
Target:	MDM2[1]
In Vivo:	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.
In Vitro:	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).
References:	[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.