title: Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.
abstract: Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.
authors.affiliation: Chengdu Medical College, Pharmacy School, Chengdu, Sichuan Province, China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.forename: Xiurong
authors.initials: X
authors.lastname: Gao
authors.forename: Wang
authors.initials: W
authors.lastname: Zan
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D001688:Biological Products / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005454:Fluorescence Polarization / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D061986:MCF-7 Cells; D054419:Receptors, Adiponectin / Q000819:agonists* / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D001688:Biological Products; D054419:Receptors, Adiponectin