Pomerantz talks about submicromolar inhibitors in ACS podcast

Professor William Pomerantz' lab has reported an improved screening methodology for small molecule discovery against a class of transcription factors called bromodomains, which was published this month in ACS Chemical Biology 2015, 10, 2246-56. Pomerantz also talked about this research in ACS Chemical Biology's monthly podcast, starting at 5 minutes, 30 seconds.

Despite enthusiasm for targeting bromodomains for therapeutic intervention, discovery of selective molecules that discriminate the binding sites amongst the 61 different bromodomains still poses a significant challenge.

In this study, led by fourth-year graduate student Andrew Urick, protein-observed ¹⁹F NMR methods were used to screen more than 200 small molecules against two similar bromodomains, called Brd4 and BPTF. Results from this study led to submicromolar inhibitors for Brd4 as potential anticancer agents as well as the first inhibitors for BPTF.

Their new small molecule, called AU1, is being optimized for studying its role in affecting cancer and heart disease with collaborators Professpr Camila dos Santos from the Cold Spring Harbor Laboratory, and Professor Jennifer Hall from the University of Minnesota's Lillehei Heart Institute. Chemical Engineering undergraduate Melissa Cassel was also a co-author.

Figure: Dual Protein Screening by PrOF NMR identifies selective small molecules for Brd4 and BPTF. Figure published earlier this year in American Chemical Society Chemical Biology.