The Koehler Lab aims to innovate in the earliest stages of drug discovery by building chemical tools or technologies to assist in the process of target validation and by expanding the repertoire of protein targets that are considered to be druggable. We focus primarily on building chemical tools and methods for studying temporal aspects of transcriptional regulation in development and disease with a focus on cancer.

Compound that targets Class II deacetylases

The Koehler lab has an interest in developing probes of enzymes that regulate post-translational modifications of oncogenic transcription factors including the enzymes that govern acetylation status. Acetyl marks regulate the activity of transcription factors through several mechanisms, often by enhancing DNA-binding capacity or affecting protein stability. Our lab is developing compounds that reversibly target reactive Cys residues in the zinc-dependent lysine deacetylases that regulate acetylation status of several transcription factors. Here we show a compound that targets Class II deacetylases, which was discovered using a high-throughput binding assay involving small-molecule microarrays (Boskovic et al., ACS Chemical Biology, 2016).