Abstract: Screening methods as well as kits for identifying compounds capable of trapping proteins, e.g. proteins involved in DNA repair, are provided. The methods provide the use of live-cell imaging and local laser micro-irradiation of nuclear DNA in an assay to measure the effects of compounds on the trapping of 5 proteins on DNA. The disruption, e.g. inhibition, of specific proteins, such as poly-(ADP-ribose) polymerases or ALC1 enzyme, leads to trapping on chromatin and/or at DNA damage sites. This inhibits essential cellular functions, e.g. DNA damage repair, and can potentiate cancer cell killing.

Abstract: The present invention relates to small molecule compounds that allosterically inhibit ALC1 (CHD1L) and which induce the trapping of PARP1, PARP2 and/or PARP3 on chromatin or at DNA damage sites. Disruption of the chromatin remodeling forces of ALC1 through these agents enables a highly selective therapy for targeting the DNA damage functions of PARP enzymes in several proliferative diseases, notably BRCA-deficient cancers. Via inhibition of the enzymatic activity, the compounds engage the synthetic lethality between BRCA1/2 and ALC1. By trapping PARP enzymes, inhibitors of ALC1 potentiate the cancer cell killing properties of PARP inhibitors, enable therapeutic approaches where ALC1 is amplified as an oncogene, therapeutically make it possible to overcome PARP inhibitor resistance mechanisms and enable an alternative approach to the treatment of germline or acquired BRCA1/BRCA2 deficiency, including tumors defined by “BRCAness” or other changes in DNA repair networks.

Abstract: The present invention relates to methods for determining a binding and/or functional interaction of a protein of interest with a nucleosomal substrate wherein at least one of the histone types of the nucleosomal substrate has a homogenous post-translational modification pattern. Further, the invention relates to nucleosomal substrates, wherein at least one of the histone types of the nucleosomal substrate has a homogenous post-translational modification pattern, and to methods for providing such nucleosomal substrates.

Abstract: This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula (I), (II), (IIa), (III), (IV), (V), or (VI)) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.

Abstract: This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula (I), (II), (IIa), (III), (IV), (V), or (VI)) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.

Abstract: The present invention relates to methods for determining a binding and/or functional interaction of a protein of interest with a nucleosomal substrate wherein at least one of the histone types of the nucleosomal substrate has a homogenous post-translational modification pattern. Further, the invention relates to nucleosomal substrates, wherein at least one of the histone types of the nucleosomal substrate has a homogenous post-translational modification pattern, and to methods for providing such nucleosomal substrates.