Described are dual mass-spectrometry-cleavable cross-linkers that can be cleaved selectively using two differential tandem mass-spectrometric techniques such as collision induced dissociation (CID) or electron transfer dissociation (ETD), i.e., a dual cleavable crosslinking technology (DUCCT) cross-linker. When used to cross-link a macromolecule, such as a peptide, MS/MS fragmentation produces two signature complementary mass spectra of same cross-linked peptides, the analysis of which gives rise to high confidence in characterizing the structures of the cross-linked macromolecules as well as sites of interactions. Also described, are methods of making and using DUCCT cross-linkers.

The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

The present disclosure relates to methods of inhibiting vimentin activity, methods of screening for new vimentin inhibitors and uses of new vimentin inhibitors.

The invention relates to macrocyclic peptides and pharmaceutical compositions thereof. The invention further relates to pharmaceutical compositions for modulating opioid receptor activity.

The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.

Disclosed are various prodrugs of L-Phe-D-Arg-L-Phe-L-Lys-NH.sub.2.

Unique compounds useful for inhibiting a proteasome in a cell, pharmaceutical compositions and methods of their use are provided herein.

The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R.sub.1, R.sub.1, R.sub.1, R.sub.1, R.sub.1, R.sub.1, R.sub.1, R.sub.1, R.sub.1, X.sub.1, X.sub.2, and X.sub.3 are described herein.

The present technology provides compounds of Formula I (or pharmaceutically acceptable salts and/or solvates thereof) that are useful in treating a CNS-related disorder such as schizophrenia, schizoaffective disorder, migraine, depression, pain, drug addiction, drug use, and/or drug seeking behavior. Also provided are compositions, medicaments, and methods including such compounds. ##STR00001##

Disclosed herein is a cyclic peptide polymer. R.sup.1, R.sup.2, and R.sup.3 are organic groups. Each R.sup.4 is a covalent bond, methylene, ethylene, n-propylene, or n-butylene. Each X is —NH—, —O—, or —O—CO—. The values m and n are nonnegative integers having a sum of at least 1. The value p is an integer greater than 1. The cyclic peptide polymer may be made by providing a first cyclic peptide monomer having a protecting group on the X group, covalently binding the —CO—OH group of the first cyclic peptide monomer to a solid support having a carboxylic acid-reactive group, converting the protecting group to —XH, reacting the —XH group with the —CO—OH group of an additional cyclic peptide monomer, optionally repeating the converting and reacting steps with further additional cyclic peptide monomers, and cleaving the cyclic peptide polymer from the solid support. ##STR00001##