Protein tyrosine phosphatase 1B inhibitors for the treatment of type 2 diabetes and obesity: recent advances.
This review outlines the physiology of protein tyrosine phosphatase 1B (PTP1B) and its potential involvement in the states of insulin resistance that characterizes both obesity and type 2 diabetes. The primary focus of this review is upon the elucidation of the role and control of PTP1B enzyme activity in obesity and type 2 diabetes. Furthermore, since selectivity and cell permeability are the two most important requirements for the development of successful PTP1B inhibitors, recent progress in finding compounds meeting these criteria are discussed.
Harley
Elizabeth A
EA
Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France. elizabeth.harley@fr.netgrs.com
Levens
Nigel
N
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013379:Substrate Specificity
D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D016376:Oligonucleotides, Antisense; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse