Selective inhibition of PARP10 using a chemical genetics strategy.
Basic Information
ID: ALA3627698
Journal: Bioorg Med Chem Lett
Title: Selective inhibition of PARP10 using a chemical genetics strategy.
Authors: Morgan RK, Carter-O'Connell I, Cohen MS.
Abstract: The lack of inhibitors that are selective for individual poly-ADP-ribose polymerase (PARP) family members has limited our understanding of their roles in cells. Here, we describe a chemical genetics approach for generating selective inhibitors of an engineered variant of PARP10. We synthesized a series of C-7 substituted 3,4-dihydroisoquinolin-1(2H)-one (dq) analogues designed to selectively inhibit a mutant of PARP10 (LG-PARP10) that contains a unique pocket in its active site. A dq analogue containing a bromo at the C-7 position demonstrated a 10-fold selectivity for LG-PARP10 compared to its WT counterpart. This study provides a platform for the development of selective inhibitors of individual PARP family members that will be useful for decoding their cellular functions.
CiteXplore: 26231158
DOI: 10.1016/j.bmcl.2015.07.033
Patent ID: ┄