SCREENING ASSAY FOR IDENTIFICATION OF POLY(ADP-RIBOSE) POLYMERASE 1 INHIBITORS

摘要

Screening methods as well as systems and kits for identifying inhibitors of DNA-independent, histone H4-dependent activation of PARP-1 are provided. The methods comprise screening molecules for their capacity to inhibit the activation and/or biologic activity of PARP-1, as measured by poly(ADP)-ribose production from nicotinamide adenine dinucleotide. PARP-1 inhibitors identified through the screening methods may be used to treat cancer in which PARP-1 activation or biologic activity plays a role.

主权项

1. A method for screening a compound for capability to inhibit poly(ADP-ribose) polymerase 1 (PARP-1), comprising contacting PARP-1 or a portion of PARP-1 comprising the catalytic domain with the core histone H4 in the presence of the compound and nicotinamide adenine dinucleotide, and determining the level of H4-dependent biologic activity of the PARP-1 or a portion of PARP-1 comprising the catalytic domain in the presence of the compound relative to the level of H4-dependent biologic activity of the PARP-1 or a portion of PARP-1 comprising the catalytic domain in the absence of the compound.