MSI-1436

• CAT Number: I002401
• CAS Number: 186139-09-3
• Molecular Formula: C37H72N4O5S
• Molecular Weight: 685.06
• Purity: ≥95%
• Target: PTP-1B
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IC50: 1 μM
• 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([C@H](OS(=O)(O)=O)CC[C@H]([C@H]1CC[C@H]2[C@@H]3[C@@H](C[C@H]4C[C@@H](NCCCNCCCCNCCCN)CC[C@@]4([C@H]3CC[C@]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.

Reference

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.