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 is directed to compounds that specifically target DUSP5 and act as antagonists of that enzyme. Such compounds are useful in the treatment of various conditions including, but not limited to vascular anomalies, cancer, and macular degeneration.

Disclosed are peptide conjugates comprising an active agent, a spacer moiety, and a dimeric collagen hybridizing peptide comprising a first and second collagen hybridizing peptide, a linker; and a branch point, wherein the first and second collagen hybridizing peptides comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12. Also disclosed are methods of detecting denatured collagen in a sample comprising contacting a composition comprising any one of the disclosed peptide conjugates to a sample, wherein the active agent comprises a therapeutic agent, and detecting the presence or absence of binding of the peptide conjugate to denatured collagen, the presence of binding indicating the presence of denatured collagen in the sample. Also disclosed are methods of treating a disease or injury involving collagen damage comprising administering to a subject having a disease or injury involving collagen damage any one of the disclosed peptide conjugates.

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.

Based on the discovery that MBLAC1 is a specific, high-affinity target for Ceftriaxone (Cef), MBLAC1 may be used for identifying treatments for addiction to substances of abuse. Methods for identifying therapeutic agents for treatment of addiction to a substance of abuse include using an assay to determine if a test agent is capable of binding to MBLAC1 or disrupting binding between MBLAC1 protein and Cef, and identifying such a test agent as a candidate therapeutic agent for treatment of addiction to a substance of abuse. MBLAC knock-out (KO) animals, methods of use thereof, and kits are used for identifying a therapeutic agent that reduces the actions of at least one substance of abuse. Methods also include using cellular extracts from tissue or cultured cells taken from wild-type (WT) MBLAC1 and MBLAC1 KO animals for screening for novel, Cef-like molecules in vitro, and using cells from a MBLAC1 KO animal to test for Cef-like actions of a test molecule.

The disclosure provides compositions comprising at least one assembly comprising a peptide and a major histocompatibility complex (MHC), wherein the peptide is an integral component of the MHC, wherein the peptide is attached to a surface at its C-terminus through a linker and wherein the peptide is synthesized on the surface. In certain embodiments, the compositions comprise a plurality of assemblies in a spatially-ordered array. The disclosure provides methods for making and using these compositions.

The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of SAMTOR, as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity.

The present invention is based, in part, on the discovery of monoclonal and polyclonal antibodies that specifically bind to phosphorylated PD-1, as well as immunoglobulins, polypeptides, nucleic acids thereof, and methods of using such antibodies for diagnostic, prognostic, and therapeutic purposes.

In some aspects, the disclosure provides methods for modulating mitochondrial transport of serine in a cell, the methods comprising modulating expression or activity of one or more sideroflexins. In some aspects, methods of identifying agents that modulate sideroflexin expression or activity are provided. In some aspects, methods of treating cancer are provided.