Deciphering modern glucocorticoid cross-pharmacology using ancestral corticosteroid receptors.

ABSTRACT: Steroid receptors (SRs) are the largest family of metazoan transcription factors and control genes involved in development, endocrine signaling, reproduction, immunity, and cancer. The entire hormone receptor system is driven by a molecular switch triggered by the binding of small lipophilic ligands. This makes the SRs ideal pharmaceutical targets, yet even the best clinically approved synthetic steroidal agonists are prone to cross-reactivity and off-target pharmacology. The mechanism underlying this promiscuity is derived from the fact that SRs share common structural features derived from their evolutionary relationship. More often than not, rational attempts to probe SR drug selectivity via mutagenesis fail even when high quality structural and functional data are available due to the

SUBMITTER: Kohn JA 

PROVIDER: S-EPMC3351298 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature