This work provides reagents to develop specific inhibitors of the macrodomains of PARP14, for potential use for cancer and/or inflammation. Targeting the macrodomains of PARP14 is an alternative targeting strategy to PARP catalytic domain inhibitors that may allow greater inhibitor selectivity, and an alternative cellular effect. This package includes protein purification protocols, crystal structures of the 2nd and 3rd macrodomain of PARP14 in complex with small molecule chemical starting points, in vitro assays to measure ligand binding to the macrodomains, as well as validation of a PARP14 antibody and reagents to generate PARP14 knock-out cell lines (CRISPR-Cas9).

Future versions of this document will contain experimental data on the PARP14 TEP.