Protein tyrosine phosphatase 1B inhibition: opportunities and challenges.
Protein tyrosine phosphatase 1B (PTP1B) has been implicated as one of the key negative regulators of insulin and leptin signal transduction pathways. PTP1B deficient mice are more sensitive to insulin, and have improved glycemic control and resistance to diet-induced obesity than the wild-type control mice. Inhibiting PTP1B action using antisense oligonucleotides and small molecule inhibitors represents novel therapeutic approach for the treatment of insulin resistance, type II diabetes, and obesity. The rapid development of this field is evidenced by the increasing number of patents and publications in recent years. This review will highlight the recent advances in various approaches for attenuating PTP1B action, particularly small molecule PTP1B inhibitors, and the challenges associated with developing PTP1B inhibitors with drug like properties.
Liu
Gang
G
Metabolic Disease Research, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. gang.liu@abbott.com
D000085:Acetates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D018716:Molecular Mimicry; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology; D019000:Phosphotyrosine / Q000737:chemistry / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000085:Acetates; D001565:Benzoates; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D016376:Oligonucleotides, Antisense; D063065:Organophosphonates; D012459:Salicylates; C084037:dephostatin; D019000:Phosphotyrosine; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C415326:phenoxyacetic acid