The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Compounds and compositions are disclosed in which a quaternized drug unit is linked to a targeting ligand unit from which a tertiary amine-containing drug is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed.

The compounds of the present invention are represented by the following compounds having Formula (I) and Formula (I′): where the substituents R, R.sup.1, R.sup.3 R.sup.4, R′, W, X, Y, Z, k, and m are as defined herein and where the substituents R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, Y, Z, and m are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues. ##STR00001##

The compounds of the present invention are represented by the following compounds having Formula (I) and Formula (I′): where the substituents R, R.sup.1, R.sup.3 R.sup.4, R′, W, X, Y, Z, k, and m are as defined herein and where the substituents R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, Y, Z, and m are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues. ##STR00001##

The present invention provides a method for obtaining a specifically-shaped crystal (specifically, spherocrystal) of a compound with good reproducibility. This method for producing a specifically-shaped crystal (specifically spherocrystal) of a compound comprises: (1) a step for preparing a supersaturated solution of a compound having a degree of supersaturation equal to or higher than a critical degree of supersaturation; and (2) a step for precipitating a specifically-shaped crystal (specifically spherocrystal) of a compound from the supersaturated solution.

A SMAC mimetic and pharmaceutical compositions thereof and methods of use.

A SMAC mimetic and pharmaceutical compositions thereof and methods of use.

A number of anti-angiogenic strategies connected with the VEGF signalling pathway are used in current clinical treatment or trial phase, but they either cause adverse effects or are not specific. Various strategies were aimed at identifying peptides inhibiting the VEGF-A.sub.165/NRP-1 interaction. A well-known antiangiogenic peptide is the heptapeptide termed “A7R” having the amino acid sequence ATWLPPR, for which various derivatives have been synthesized, which include peptides having the general sequence Lys(hArg)-AA.sup.2-AA.sup.3-Arg. However, the ability of the known peptides to inhibit the VEGF-A.sub.165/NRP-1 interaction was too low for their use as candidate drugs for inhibiting angiogenesis in subjects in need thereof. The present inventors have now conceived a family of novel peptide-like compounds having a nanomolar affinity for NRP-1, which are thus endowed with a powerful capacity to inhibit the VEGF-A.sub.165/NRP-1 interaction. These novel peptide-like compounds may be relevantly used as antiangiogenic compounds, especially in subjects affected with cancer.

The present invention relates to a compound of formula (I), wherein X is C═O, C═S or B—OH; Y is an electrophile and Z is a leaving group, or Y═Z is an electrophile; R.sup.1 comprises or consists of (a) (i) a first group binding to a proteolytic site of a proteasome, the first group being bound to X; and (ii) optionally a second group enhancing delivery; or (b) a group binding between subunits β1 and β2 of a proteasome; R.sup.2 and R.sup.3 are independently selected from H, methyl, methoxy, ethyl, ethenyl, ethynyl and cyano, wherein methyl and ethyl may be substituted with OH or halogen. ##STR00001##

The present invention features peptides, compositions, and related methods for treating gastrointestinal disorders and conditions, including but not limited to, irritable bowel syndrome (IBS), gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional heartburn, dyspepsia, visceral pain, gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), disorders and conditions associated with constipation, and other conditions and disorders are described herein. using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor.