Recent advances in the development of small molecule inhibitors of PTP1B for the treatment of insulin resistance and type 2 diabetes.
Protein tyrosine phosphatases (PTPs) are a large family of diverse molecules that play an important role in both activating and attenuating a wide variety of cellular responses. One of these phosphatases, protein tyrosine phosphatase 1B (PTP1B), is clearly involved in attenuating insulin signaling, and much effort has been devoted towards the development of inhibitors of this enzyme as a therapeutic approach to treat insulin resistance and type 2 diabetes. This review will focus on recent advances in the development of small molecule inhibitors for PTP1B and the challenges for generating selective molecules. This review is largely limited to papers published within the last two years, since a review on this subject was published recently in this journal.
Tobin
James F
JF
Department of Metabolic Diseases, Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA. jtobin@wyeth.com
Tam
Steve
S
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends*
D011500:Protein Synthesis Inhibitors; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases