Recent progress in the steroid hormone receptor (SHR) field coupled with advances in combinatorial chemistry and high throughput screening (HTS) instrumentation have set the stage for development of more selective therapies for a broad range of cancers, metabolic diseases, and chronic conditions. To enable the drug discovery opportunities provided by these advances, PanVera is developing the robust molecular screening assays needed for identification and characterization of novel SHR ligands. In Phase I, PanVera developed fluorescence polarization (FP)-based competitive ligand binding assays for estrogen receptors alpha and beta that have been rapidly adapted for high throughput drug discovery programs at several pharmaceutical companies. In Phase II, we will develop similar FP- based ligand binding assays for additional SHRs, including wild type and mutant androgen and progesterone receptors and additional estrogen receptor isoforms. In addition, we will develop secondary FP-based assays, based on fluorescent peptides that mimic the agonist-dependent binding of transcriptional coactivators to SHRs. These secondary assays will allow pharmaceutical researchers to predict the in vivo tissue specificity and transcriptional activity of novel SHR ligands. In combination, these two HTS assay methods will provide the molecular tools needed to accelerate discovery of highly selective SHR modulators.
The Phase II SBIR studies will result in development of proprietary fluorescent steroids and FP-based HTS assays for identification and characterization of novel ligands for estrogen, androgen, and progesterone receptors. PanVera will commercialize these assays immediately as part of their CoreHTS drug discovery product line through their domestic and international drug discovery products distribution network.
