Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor delta agonists as potent anti-obesity agents in vivo.

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Ham J, Hwang H, Kim E, Kim JA, Cho SJ, Ko J, Lee W, Lee J, Holla H, Banerjee J, Kim S, Yang I, Lee HJ, Shin K, Choi H, Nam SJ, Tak J, Hahn D, Oh T, Won DH, Lee TG, Choi J, Park MS, Seok C, Chin J, Kang H

Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor delta agonists as potent anti-obesity agents in vivo.

Eur J Med Chem. 2012 Jul;53:190-202. doi: 10.1016/j.ejmech.2012.03.055. Epub 2012 Apr 6.

PubMed ID

22534184 [ View in PubMed

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Abstract

We have discovered and demonstrated the in vitro and in vivo PPARdelta-selective activity of novel Y-shaped agonists. These compounds activated hPPARdelta with EC(50) values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARdelta agonists with 10(4)-fold selectivity over the other two subtypes, namely, hPPARalpha and hPPARgamma. The PPARdelta ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cardarine	Peroxisome proliferator-activated receptor alpha	EC 50 (nM)	229	N/A	N/A	Details
Cardarine	Peroxisome proliferator-activated receptor delta	EC 50 (nM)	2.5	N/A	N/A	Details
Cardarine	Peroxisome proliferator-activated receptor delta	EC 50 (nM)	24	N/A	N/A	Details