Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist.

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Wang Y, Fang F, Wong CW

Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist.

Biochem Pharmacol. 2010 Jul 1;80(1):80-5. doi: 10.1016/j.bcp.2010.03.013. Epub 2010 Mar 16.

PubMed ID

20298676 [ View in PubMed

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Abstract

As a ligand for peroxisome proliferators-activated receptor gamma (PPAR gamma), troglitazone inhibits cell growth by mechanisms besides activating PPAR gamma. In this study, we found that troglitazone interfered with the interactions between estrogen-related receptor alpha and gamma (ERR alpha and ERR gamma) and their coactivator PPAR gamma coactivator-1 alpha (PGC-1 alpha) functioning as an inverse agonist. Additionally, troglitazone suppressed the expressions of PGC-1 alpha and its related member PGC-1 beta which are key regulators of mitochondrial function. Consequently, troglitazone reduced mitochondrial mass and suppressed the expressions of superoxide dismutases to elevate reactive oxygen species (ROS) production. The increase in ROS in turn induced the expression of cell cycle inhibitor p21(WAF1). We therefore propose that ERR alpha and ERR gamma are alternative targets of troglitazone important for mediating its growth suppressive effect.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Troglitazone	Estrogen-related receptor gamma	Protein	Humans	No	Inverse agonist	Details
Troglitazone	Steroid hormone receptor ERR1	Protein	Humans	No	Inverse agonist	Details