Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists.
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.
Mahindroo
Neeraj
N
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
Peng
Yi-Hui
YH
Lin
Chia-Hui
CH
Tan
Uan-Kang
UK
Prakash
Ekambaranellore
E
Lien
Tzu-Wen
TW
Lu
I-Lin
IL
Lee
Hong-Jen
HJ
Hsu
John Tsu-An
JT
Chen
Xin
X
Liao
Chun-Chen
CC
Lyu
Ping-Chiang
PC
Chao
Yu-Sheng
YS
Wu
Su-Ying
SY
Hsieh
Hsing-Pang
HP
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
D000085:Acetates; D007211:Indoles; D008024:Ligands; D009281:Naphthalenes; D047492:Peroxisome Proliferator-Activated Receptors; D011422:Propionates