Silencing mediator for retinoid and thyroid

Halofenic acid is a SPPARM that functions primarily as a partial agonist characterized by the differential recruitment of PPAR cofactors, i.e. displacement of corepressors [NCoR and silencing mediator for retinoid and thyroid receptors (SMRT)] and inefficient recruitment of coactivators [cAMP response element binding protein (CREB) binding protein (CBP) and TRAP220] [73]. When dosed orally to diabetic mice and rats as the acetamidoethyl ester, halofenic acid produces insulin sensitization comparable to rosiglitazone without increases in body weight. 

Konno Y, Kodama S, Moore R, Kamiya N, Negishi M (2009) Nuclear xenobiotic receptor pregnane X receptor locks corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) onto the CYP24A1 promoter to attenuate vitamin Dj activation. Mol Pharmacol 75 265-271... 

Essentially the functional counterpart of coactivators, corepressor proteins bind to many NRs in the absence of ligand and serve to repress basal transcriptive activity [62], Corepressors play a particularly important role for NRs that are found almost exclusively in the nucleus, unlike the apo steroid receptors that are cytoplasmically localized. Studies involving the nuclear-localized receptors TR and RAR led to the identification of silencing mediator of retinoid and thyroid (SMRT) receptors and nuclear receptor corepressor (NCoR) [63, 64]. Both SMRT and NCoR recruit histone deacetylases (HDACs), namely, HDAC3, which function to reverse the chromatin unwinding result of the coactivator-recruited histone acetylases [65],... 

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