MSI-1436

Appearance:Solid powder
Purity: > 98%

Cat No:	I002401
Cas No:	186139-09-3
Product-Name:	MSI-1436
InChI:	InChI=1S/C37H72N4O5S/c1-26(2)34(46-47(43,44)45)13-10-27(3)30-11-12-31-35-32(15-17-37(30,31)5)36(4)16-14-29(24-28(36)25-33(35)42)41-23-9-22-40-20-7-6-19-39-21-8-18-38/h26-35,39-42H,6-25,38H2,1-5H3,(H,43,44,45)/t27-,28-,29+,30-,31+,32+,33-,34-,35+,36+,37-/m
InChIKey:	WUJVPODXELZABP-FWJXURDUSA-N
SMILES:	CC([[email protected]](OS(=O)(O)=O)CC[[email protected]]([[email protected]]1CC[[email protected]]2[[email protected]@H]3[[email protected]@H](C[[email protected]]4C[[email protected]@H](NCCCNCCCCNCCCN)CC[[email protected]@]4([[email protected]]3CC[[email protected]]12C)C)O)C)C

MSI-1436(cas 186139-09-3) is a selective, non-competitive inhibitor of the enzyme protein tyrosine phosphatase 1B (PTB-1B), with 200-fold selective for PTP-1B (IC50=1 μM) relative to TC-PTP (IC50=224 μM).

MSI-1436 is a first-in-class allosteric PTP-1B inhibitor for the treatment of type 2 diabetes and obesity, which is a well-recognized target for a range of therapy areas. MSI-1436 significantly enhances insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) β and STAT3, direct targets of PTP1B, in HepG2 cells.

Trodusquemine (MSI-1436) causes rapid and reversible weight loss in genetic models of obesity.

1: Roitman MF, Wescott S, Cone JJ, McLane MP, Wolfe HR. MSI-1436 reduces acute food intake without affecting dopamine transporter activity. Pharmacol Biochem Behav. 2010 Nov;97(1):138-43. doi: 10.1016/j.pbb.2010.05.010. Epub 2010 May 15. PubMed PMID: 20478327; PubMed Central PMCID: PMC2945616.
2: Lantz KA, Hart SG, Planey SL, Roitman MF, Ruiz-White IA, Wolfe HR, McLane MP. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring). 2010 Aug;18(8):1516-23. doi: 10.1038/oby.2009.444. Epub 2010 Jan 14. PubMed PMID: 20075852.