Protein tyrosine phosphatases as drug targets: PTP1B and beyond.
Protein tyrosine phosphatases (PTPs) control signal transduction pathways and have recently emerged as potential drug targets. Inhibition of individual PTPs can result in the activation of therapeutically relevant kinase cascades. This is particularly useful in cases where disease is associated with hormonal resistance, such as insensitivity to insulin or leptin. Currently, PTP1B is being investigated by a number of companies as a promising target for leptin/insulin mimetics and in the treatment of diabetes and obesity. Since all 90-100 PTPs have been identified in the human genome, the challenge now is to identify the function of these enzymes and the therapeutic indications that may exist for specific PTP inhibitors.
Hooft van Huijsduijnen
Rob
R
Serono Pharmaceutical Research Institute, 14, chemin des Aulx, Plan-les-Ouates/Geneva, Switzerland. rob.hooft@serono.com
Wälchli
Sébastien
S
Ibberson
Mark
M
Harrenga
Axel
A
D002199:Capillary Permeability / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016147:Genes, Tumor Suppressor; D006801:Humans; D007107:Immune System / Q000201:enzymology; D007239:Infections / Q000188:drug therapy / Q000201:enzymology; D007328:Insulin / Q000502:physiology; D020738:Leptin / Q000502:physiology; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology; D010024:Osteoporosis / Q000188:drug therapy / Q000201:enzymology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000235:genetics / Q000502:physiology; D011946:Receptors, Antigen / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
D007328:Insulin; D020738:Leptin; D009363:Neoplasm Proteins; D011946:Receptors, Antigen; D019061:src-Family Kinases; D018844:Cyclin-Dependent Kinases; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases