title: Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: design, synthesis, structural biology, and molecular docking studies.
abstract: A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARgamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARgamma protein resulting in potent activity.
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: Chiung-Chiu
authors.initials: CC
authors.lastname: Wang
authors.forename: Chun-Chen
authors.initials: CC
authors.lastname: Liao
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Huang
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Lu
authors.forename: Tzu-Wen
authors.initials: TW
authors.lastname: Lien
authors.forename: Yi-Huei
authors.initials: YH
authors.lastname: Peng
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Huang
authors.forename: Ying-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Ming-Chen
authors.initials: MC
authors.lastname: Hsu
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Tsai
authors.forename: John T-A
authors.initials: JT
authors.lastname: Hsu
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
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: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C509004:2-(5-(3-(6-benzoyl-1-propylnaphthalene-2-yloxy)propoxy)indol-1-yl)ethanoic acid; D007210:Indoleacetic Acids; D008024:Ligands; D009281:Naphthalenes; D047495:PPAR gamma