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On the intractability of estrogen-related receptor alpha as a target for activation by small molecules.

ABSTRACT: The estrogen-related receptor alpha (ERRalpha) is a potential target for activation in the treatment of metabolic disease. To date, no small-molecule agonists of ERRalpha have been identified despite several high-throughput screening campaigns. We describe the synthesis and profiling of a small array of compounds designed on the basis of a previously reported agonist-bound crystal structure of the closely related receptor ERRgamma. The results suggest that ERRalpha may be intractable as a direct target for pharmacologic activation.

SUBMITTER: Hyatt SM

PROVIDER: S-EPMC2556064 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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On the intractability of estrogen-related receptor alpha as a target for activation by small molecules.

Hyatt Stephen M SM Lockamy Elizabeth L EL Stein Rebecca A RA McDonnell Donald P DP Miller Aaron B AB Orband-Miller Lisa A LA Willson Timothy M TM Zuercher William J WJ

Journal of medicinal chemistry 20071204 26

The estrogen-related receptor alpha (ERRalpha) is a potential target for activation in the treatment of metabolic disease. To date, no small-molecule agonists of ERRalpha have been identified despite several high-throughput screening campaigns. We describe the synthesis and profiling of a small array of compounds designed on the basis of a previously reported agonist-bound crystal structure of the closely related receptor ERRgamma. The results suggest that ERRalpha may be intractable as a direct ...[more]

PMID: 18052088

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