title: Two thiophenes compounds are partial peroxisome proliferator-activated receptor α/γ dual agonists.
abstract: In our previous study, two synthetic thiophenes such as IMB-05 and IMB-15 were found as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and exhibited beneficial effects on glucose tolerance of diabetic mice in vivo. In the present study, their effect on the transactivity of other nuclear receptors was further investigated. IMB-05 and IMB-15 could not only activated PPARγ but also efficiently activate PPARα in GAL4-hPPARα/γ (ligand binding domain (LBD)) chimeric receptor assay and PPAR response element (PPRE)-luc reporter gene assay with EC(50) values of 1.8-5.2 µM, whereas no activity was observed in other nuclear receptor assays. In addition, the maximal efficacy of IMB-05 and IMB-15 in activating PPARα/γ was approximately 30% of that observed with Wy14643 and rosiglitazone. These data indicate that the two thiophene derivatives are novel class of partial PPARα/γ dual agonists, which may be the mechanism underlying their regulatory effects on glucose homeostasis.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 10050, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Huayi
authors.initials: H
authors.lastname: Shao
authors.forename: Zongying
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lu
authors.forename: Yanni
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhuorong
authors.initials: Z
authors.lastname: Li
authors.forename: Shuyi
authors.initials: S
authors.lastname: Si
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D017930:Genes, Reporter / Q000187:drug effects; D022781:Hepatocytes; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D058990:Molecular Targeted Therapy; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics; D010957:Plasmids / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics; D000077154:Rosiglitazone; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013804:Thenoyltrifluoroacetone / Q000737:chemistry / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C572756:1-(benzo(b)thiophen-2-yl)-2-(methylsulfinyl)ethanone; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D013454:Sulfoxides; D045162:Thiazolidinediones; D013876:Thiophenes; D000077154:Rosiglitazone; D013804:Thenoyltrifluoroacetone; C006253:pirinixic acid