Identification of small molecule degraders of XPB for inflammatory diseases

National Center For Advancing Translational Sciences

Investigators

Abstract

This collaborative team aims to build on previous research by identifying small molecules that phenocopy the effect of spironolactone on XPB protein stability. XPB is a nuclear protein that regulates the production of inflammatory cytokines. During this period, the collaborative team completed high-throughput screening of more than 8,000 biologically active molecules to identify compounds that induce degradation of the XPB protein. Several compounds of interest emerged from screening, which are being further characterized. Additionally, the mechanism of action of top actives were examined using several approaches combining affinity-based probes and proteomic methods.