title: Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists.
abstract: Type 2 diabetes has rapidly reached an epidemic proportion becoming a major threat to global public health. PPAR agonists have emerged as a leading class of oral antidiabetic drugs. We report a structure biology analysis of novel indole-based PPAR agonists to explain the structure-activity relationships and present a critical analysis of reasons for change in selectivity with change in the orientation of the same scaffolds. The results would be helpful in designing novel PPAR agonists.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mahindroo
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Peng
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Uan-Kang
authors.initials: UK
authors.lastname: Tan
authors.forename: Ekambaranellore
authors.initials: E
authors.lastname: Prakash
authors.forename: Tzu-Wen
authors.initials: TW
authors.lastname: Lien
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Lu
authors.forename: Hong-Jen
authors.initials: HJ
authors.lastname: Lee
authors.forename: John Tsu-An
authors.initials: JT
authors.lastname: Hsu
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Chun-Chen
authors.initials: CC
authors.lastname: Liao
authors.forename: Ping-Chiang
authors.initials: PC
authors.lastname: Lyu
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wu
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
mesh_terms: D000085:Acetates / Q000737:chemistry; D000478:Alkylation; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000737:chemistry* / Q000235:genetics; D011422:Propionates / Q000737:chemistry; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000085:Acetates; D007211:Indoles; D008024:Ligands; D009281:Naphthalenes; D047492:Peroxisome Proliferator-Activated Receptors; D011422:Propionates