Screening assay for identification of poly(adp-ribose) polymerase 1 inhibitors
AssigneeInstitute for Cancer Research d/b/a The Research Institute of Fox Chase Cancer Center
InventorAlexei Tulin
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Abstract
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.
Claims21
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.
A method for determining poly(ADP-ribose) polymerase 1 (PARP-1) in a sample, comprising contacting the sample with the core histone H4 in the presence of nicotinamide adenine dinucleotide, and determining the level of H4-dependent biologic activity of PARP-1 in the sample.
A method for determining the synthesis of poly(ADP-ribose) in a sample comprising poly(ADP-ribose) polymerase 1 (PARP-1), comprising contacting the sample with the core histone H4 in the presence of nicotinamide adenine dinucleotide, quantifying the level of poly(ADP)-ribose in the sample.
Dependencies are inferred from the claim text.