Provided herein are nicotinamide adenine dinucleotide analogues, compositions comprising such compounds, and methods of using such analogues and compositions.

Mutant mono ADP-ribose-polymerases (mono-PARP) proteins and small molecule compound substrates specific for the mutant mono-PARP proteins as well as methods of using these compositions to identify protein targets of the mono-PARPs and to screen for antagonists of the mono-PARPs are described.

The present disclosure relates to compounds of Formula I and II, wherein R.sup.1-R.sup.20 and FL are defined herein. Also provided are methods of targeting alpha-radiation to poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, reducing proliferation of cancer cells, reducing proliferation of cancer cells, detecting intact and enzymatically active poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, detecting PARP-1 enzyme expression in a subjects tissue sample, monitoring cancer treatment in a subject, or detecting a PARP-1 receptive cancer in a subject.

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Lateral flow devices, methods and kits for performing lateral flow western blot assays are provided.

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.

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.

The present disclosure is related to methods of identifying Poly(ADP-ribose) polymerases (PARP) inhibitors, and the methods of using PARP probes.

Improved methods for treating cancer are provided herein by determining if a cancer patient, particularly a colon cancer patient or a gastric cancer patient, will clinically respond in a favorable manner to a therapeutic strategy comprising the FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) or a combination of capecitabine and cisplatin. Diagnostic methods for measuring the OPRT, TYMP, and/or UCK2 proteins in a tissue sample, such as a tumor sample, from the patient are provided.

Methods for diagnosis and treatment of COVID-19 acuity in a subject include the identification of a subject as having Nan increased expression level and/or activity of thymidine phosphorylase in a biological sample obtained from the subject. An effective amount of a therapeutic agent that reduces the expression level or activity of thymidine phosphorylase can the be administered to the subject.

It is an aim of the present invention to provide inhibitors of human diphtheria toxin-like ADP-ribosyltransferases, such as ARTD10, for use as a medicine. It is another aim of the invention to provide compounds for use as human mono-ADP-ribosyltransferase (mARTD) inhibitors in vitro. In the present invention, it has been discovered that human ARTD10, which belongs to an enzyme family linked to cancer biology, can be specifically inhibited by the benzamide comprising compounds disclosed in the invention, such as 4,4-oxydibenzamide.