title: Pharmacological effects of JTT-551, a novel protein tyrosine phosphatase 1B inhibitor, in diet-induced obesity mice.
abstract: Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIO mice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIO mice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity.
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Makoto
authors.identifier: 0000-0003-3327-4190
authors.initials: M
authors.lastname: Ito
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Sumiaki
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Sakata
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Hisayo
authors.initials: H
authors.lastname: Morinaga
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000628:therapy; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: C556903:(((5-(1,1-dimethylethyl)thiazol-2-yl)methyl)(((4-(4-(4-(1-propylbutyl)phenoxy)methyl)phenyl)thiazol-2-yl)methyl)amino)acetic acid; D001786:Blood Glucose; D020738:Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D013844:Thiazoles; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse; D005947:Glucose; D005998:Glycine