Development of an ultrafiltration mass spectrometry based screening assay for ligands of human RXR(alpha)

摘要

Retinoid X receptors (RXRs) are nuclear receptors that function as ligand activated transcription factors. RXRs are obligatory components of a large number of nuclear receptor heterodimers. RXRs function as master regulators of gene expression that affect diverse physiological responses including the important cancer prevention responses of cell proliferation, inflammation, cell differentiation, and apoptosis. Thus, RXRs represent important targets for cancer chemoprevention. Previously in our laboratory, ultrafiltration mass spectrometry was invented and developed for the screening of combinatorial libraries and natural product extracts in order to identify ligands for adenosine deaminase, dihydrofolate reductase, cyclooxygenase-2, and estrogen receptors. In this study, an ultrafiltration mass spectrometry based assay was developed for the screening of natural product extracts and combinatorial libraries for the discovery of ligands to human RXR(alpha) that might be useful as drugs or drug leads for cancer chemoprevention.