The presently claimed subject matter concerns methods and kits for identifying agents that reduce binding of a clostridial neurotoxin to synaptic vesicle glycoprotein 2 (SV2).

An agent according to the present invention comprises as an effective component any of (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate; (2) a pharmaceutically acceptable salt of (1); or (3) a solvate of (1) or (2), and is used for inhibition of interaction between CR2B or CCR5 and FROUNT protein, inhibition of macrophages, control of cells constituting a cancer microenvironment or inflammatory microenvironment, or enhancement of anticancer activity of an anticancer drug. It is also possible to provide a compound with a reduced side effect and an increased pharmacological effect by identifying a disulfiram derivative having a lower aldehyde dehydrogenase-inhibiting activity and a higher FROUNT-inhibiting activity among derivatives prepared by structural modification of disulfiram.

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.

Compositions and methods for characterizing cancer cells by determining a marker of PGK1 activity. For example, methods are provided for predicting a patient response to a PGK1 inhibitor, a MEK/ERK inhibitor, an EGFR inhibitor, or a PIN1 inhibitor therapy. Methods for treating patients with such therapies are likewise provided.

The present invention relates to an antiviral composition and a screening method thereof for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that occurred in Wuhan, China in 2019. An extract from leaves or unfertilized female flowers of Cannabis sativa L. or its fraction, and the cannabinoids (CBDs) molecules isolated from it have high binding strength and stability to SARS-CoV-2 MP.sup.pro, thereby inhibiting its action as the main protease, to provide a useful lead molecule that can be used alone or in combination with other drugs to treat SARS-CoV-2.

The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.

This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid β-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid β-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

Embodiments of the present invention relate to use of a GP73 inhibitor in preparation of a drug for treating diabetes. In the embodiments of the present invention, the inventor finds that GP73 plays a key role in blood glucose regulation, and in particular, finds that soluble GP73 can specifically bind to glucagon to form a complex, enhances the blood glucose-rising function and gluconeogenesis function of glucagon and prolongs the half-life of glucagon; and finds soluble GP73 can activate the glucose production in liver and/or kidney and a gluconeogenesis signaling pathway in a glucagon-independent manner. Based on the blood glucose regulation effect of the GP73 described above, the inventor also proves through animal experiments: the GP73 inhibitor can reduce the blood glucose level and glycated hemoglobin level of diabetic mice and have a protective effect on islet β cells, and thereby having the effect of treating diabetes.

Provided herein are compositions and methods for assessing arrestin-dependent signaling. The provided compositions include fusion proteins comprising arrestin polypeptides that bind strongly to G protein-coupled receptors (GPCRs). In some instances, the fusion proteins may also bind to non-GPCR proteins, such as single transmembrane receptors and non-receptor proteins. Also provided are nucleic acids, vectors, constructs, and host cells that encode or express such fusion proteins. Also provided are methods of using such fusion proteins to assess arrestin trafficking, localization, and other functions including, for example, arrestin-mediated GPCR signaling as well as non-GPCR protein activity or signaling.

The invention relates to compounds and methods for restoring or preserving cholesterol efflux in a cell infected with Human Immunodeficiency Virus (HIV) by preventing or decreasing an interaction between Negative Regulatory Factor (Nef) protein and Calnexin protein, and methods for screening for such compounds.