Halofenic acid

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. 

The class of a-aryloxy hydratropic acid derivatives (see Table 4) combines the characteristics of the clofibrate and the halofenate structure. Surprisingly, this slight modification of the basic structure caused a striking increase in activity. Compound 47, structurally most closely related to clofibrate, showed a spectrum of activity, which was superior to that of clofibrate (factor 5—10). Impressive also was the higher activity of compound 53 against Su-13.437 2. The advantage of compounds 48-52 was similarly clear. Several representatives selected from this series were prepared for a clinical trial. 

W.S. Aronow, P.R. Harding, M. Khursheed, J.S. Vangrow and N.P. Papageorges. Effect of halofenate on serum uric acid. Clin. Pharmacol. Therap. 1 371-373 (1973) ... 

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