Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: design, synthesis, structural biology, and molecular docking studies.

Article Details

Citation

Mahindroo N, Wang CC, Liao CC, Huang CF, Lu IL, Lien TW, Peng YH, Huang WJ, Lin YT, Hsu MC, Lin CH, Tsai CH, Hsu JT, Chen X, Lyu PC, Chao YS, Wu SY, Hsieh HP

Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: design, synthesis, structural biology, and molecular docking studies.

J Med Chem. 2006 Feb 9;49(3):1212-6.

PubMed ID
16451087 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Peroxisome proliferator-activated receptor gammaP37231Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
2-{5-[3-(6-BENZOYL-1-PROPYLNAPHTHALEN-2-YLOXY)PROPOXY]INDOL-1-YL}ETHANOIC ACIDPeroxisome proliferator-activated receptor gammaIC 50 (nM)50N/AN/ADetails
2-{5-[3-(7-PROPYL-3-TRIFLUOROMETHYLBENZO[D]ISOXAZOL-6-YLOXY)PROPOXY]INDOL-1-YL}ETHANOIC ACIDPeroxisome proliferator-activated receptor gammaIC 50 (nM)152N/AN/ADetails
RosiglitazonePeroxisome proliferator-activated receptor alphaIC 50 (nM)>10000N/AN/ADetails
RosiglitazonePeroxisome proliferator-activated receptor gammaIC 50 (nM)92N/AN/ADetails