1. Structure-guided design and characterization of a clickable, covalent PARP16 inhibitor
- Author
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Daniel S. Bejan, Sunil Sundalam, Haihong Jin, Rory K. Morgan, Ilsa T. Kirby, Ivan R. Siordia, Barr Tivon, Nir London, and Michael S. Cohen
- Subjects
General Chemistry - Abstract
PARP16-the sole ER-resident PARP family member-is gaining attention as a potential therapeutic target for cancer treatment. Nevertheless, the precise function of the catalytic activity of PARP16 is poorly understood. This is primarily due to the lack of inhibitors that are selective for PARP16 over other PARP family members. Herein, we describe a structure-guided strategy for generating a selective PARP16 inhibitor by incorporating two selectivity determinants into a phthalazinone pan-PARP inhibitor scaffold: (i) an acrylamide-based inhibitor (DB008) designed to covalently react with a non-conserved cysteine (Cys169, human numbering) in the NAD
- Published
- 2022
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