Toward the discovery of small molecule PTP1B inhibitors for the treatment of metabolic diseases

✍ Scribed by Andrew J. Nichols; Robert D. Mashal; Bork Balkan

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 203 KB
• Volume: 67
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.20122

✦ Synopsis

Abstract

PTP1B is a protein tyrosine phosphatase involved in insulin and leptin signaling and is a primary mechanism for down‐regulating both the insulin and leptin receptor signaling pathways. Animals deficient in PTP1B have improved glucose regulation and lipid profiles and are resistant to weight gain when treated with a high fat diet. Thus, PTP1B inhibitors are expected to be useful in the treatment of type 2 diabetes, obesity, and the metabolic syndrome. Progress toward the design of potent and orally active PTP1B inhibitors has been hindered by the highly charged nature of the tyrosine phosphate mimetics used to date. Recent progress in the design of more drug‐like molecules holds promise for the eventual discovery and development of clinically useful PTP1B inhibitors. Drug Dev. Res. 67:559–566, 2006. © 2006 Wiley‐Liss, Inc.