title: Chirality Influence of Zaltoprofen Towards UDP-Glucuronosyltransferases (UGTs) Inhibition Potential.
abstract: Zaltoprofen (ZLT) is a nonsteroidal antiinflammation drug, and has been clinically employed to treat rheumatoid arthritis, osteoarthritis, and other chronic inflammatory pain conditions. The present study aims to investigate the chirality influence of zaltoprofen towards the inhibition potential towards UDP-glucuronosyltransferases (UGTs) isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation system was employed to investigate the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT isoforms. The inhibition difference capability was observed for the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT1A8 and UGT2B7, but not for other tested UGT isoforms. (R)-zaltoprofen exhibited noncompetitive inhibition towards UGT1A8 and competitive inhibition towards UGT2B7. The inhibition kinetic parameters were calculated to be 35.3 μM and 19.2 μM for UGT1A8 and UGT2B7. (R)-zaltoprofen and (S)-zaltoprofen exhibited a different inhibition type towards UGT1A7. Based on the reported maximum plasma concentration of (R)-zaltoprofen in vivo, a high drug-drug interaction between (R)-zaltoprofen and the drugs mainly undergoing UGT1A7, UGT1A8, and UGT2B7-catalyzed glucuronidation was indicated.
authors.affiliation: First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jia
authors.affiliation: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Cuimin
authors.initials: C
authors.lastname: Hu
authors.affiliation: College of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.
authors.forename: Haina
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Tianjin Medical University, Heping District, Tianjin, People's Republic of China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Liu
authors.affiliation: First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, People's Republic of China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Yangzhou University, Yangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, People's Republic of China.
authors.forename: Li-Xuan
authors.initials: LX
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, People's Republic of China.|Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, People's Republic of China.|Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, People's Republic of China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cao
authors.affiliation: Department of Toxicology, School of Public Health, Tianjin Medical University, Heping District, Tianjin, People's Republic of China.|Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, People's Republic of China.
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Fang
mesh_terms: D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D015394:Molecular Structure; D011422:Propionates / Q000737:chemistry* / Q000494:pharmacology*; D020033:Protein Isoforms; D013237:Stereoisomerism
chemical_list: D001578:Benzopyrans; D004791:Enzyme Inhibitors; D011422:Propionates; D020033:Protein Isoforms; C043940:pyranoprofen; D014453:Glucuronosyltransferase; C454320:UDP-glucuronosyltransferase, UGT1A8
keywords: UDP-glucuronosyltransferases (UGTs); chirality; inhibition potential; zaltoprofen