2. Academic Validation
  3. Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1

Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1

  • J Med Chem. 2006 Nov 16;49(23):6652-5. doi: 10.1021/jm060990k.
Richard J Whitby 1,  Sally Dixon,  Patrick R Maloney,  Philippe Delerive,  Bryan J Goodwin,  Derek J Parks,  Timothy M Willson
Affiliations

Affiliation

  • 1 School of Chemistry, University of Southampton, Southampton, HANTS, SO17 1BJ, UK.
PMID: 17154495 DOI: 10.1021/jm060990k
Abstract

We report the identification of substituted cis-bicyclo[3.3.0]-oct-2-enes as small molecule agonists of subfamily V orphan nuclear receptors (NR5A), liver receptor homolog-1 (LRH-1) and steroidogenic factor-1 (SF-1). Using fluorescence resonance energy transfer (FRET)-based biochemical assays, compound 5a (GSK8470) was identified as a high-affinity ligand for LRH-1 and SF-1. In liver cells, 5a increased the expression of the LRH-1 target gene small heterodimer partner (SHP). Synthesis of analogues modified at three positions led to the development of compounds with functional selectivity between LRH-1 and SF-1.

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