Abstract: Site-specific isotopically-labeled valine, leucine, and isoleucine and biosynthetic precursors for these amino acids are provided. The amino acids are labeled with 13C or 14C at the methyl group carbon atom(s) most remote from the carboxyl group. Also disclosed are the biochemical precursors of these labeled amino acids, 2-keto-4-(nC)butyric acid and 2-keto-3-(nC-methyl)-4-(nC)-butyric acid in which n, at each occurrence, is 13 or 14. Also disclosed are proteins, protein fragments, and polypeptides containing these site-specifically isotopically labeled amino acids, and methods for preparing the biochemical precursors, the amino acids, and the proteins, protein fragments, and polypeptides.

Abstract: N-Benzoyl arylsulfonamides having the formula 1

Abstract: A method of killing cancer cells comprising inhibiting the function of a gene selected from the group consisting of CDK8, STK33, PRKCM, PRKACA, ACVR1B, CDK5R1, CDC42BPB, MPP6, and CDC42BPA; pharmaceutical compositions comprising an inhibitor of the same, and a method of detecting cellular hyperplasia.

Abstract: A method of killing cancer cells comprising inhibiting the function of a gene selected from the group consisting of CDK8, STK33, PRKCM, PRKACA, ACVR1B, CDK5R1, CDC42BPB, MPP6, and CDC42BPA; pharmaceutical compositions comprising an inhibitor of the same, and a method of detecting cellular hyperplasia.

Abstract: Site-specific isotopically-labeled valine, leucine, and isoleucine and biosynthetic precursors for these amino acids are provided. The amino acids are labeled with 13C or 14C at the methyl group carbon atom(s) most remote from the carboxyl group. Also disclosed are the biochemical precursors of these labeled amino acids, 2-keto-4-(nC)butyric acid and 2-keto-3-(nC-methyl)-4-(nC)-butyric acid in which n, at each occurrence, is 13 or 14.

Abstract: N-Benzoyl arylsulfonamides having the formula: are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.

Abstract: Site-specific isotopically-labeled valine, leucine, and isoleucine and biosynthetic precursors for these amino acids are provided. The amino acids are labeled with 13C or 14C at the methyl group carbon atom(s) most remote from the carboxyl group. Also disclosed are the biochemical precursors of these labeled amino acids, 2-keto-4-(nC)butyric acid and 2-keto-3-(nC-methyl)-4-(nC)-butyric acid in which n, at each occurrence, is 13 or 14.

Abstract: N-Benzoyl arylsulfonamides having the formula 1

Abstract: N-Benzoyl arylsulfonamides having the formula 1

Abstract: Methods of detecting binding of a putative ligand to a 13C-enriched target molecule, methods of screening for compounds which bind to a 13C-enriched target molecule, methods for calculating the dissociation constant of a ligand compound which binds to a 13C-enriched target molecule, and methods employed in the determination of the specific amino acids in a 13C-enriched target molecule affected by the binding of a ligand, as well as compounds identified by these screening methods, are provided herewith.

Abstract: Compounds having the formula and pharmaceutically acceptable salts and prodrugs thereof are matrix metalloproteinase inhibitors. Also disclosed are matrix metalloproteinase-inhibiting compositions and methods of inhibiting matrix metalloproteinase in a mammal.

Abstract: Methods of detecting binding of a putative ligand to a 13C-enriched target molecule, methods of screening for compounds which bind to a 13C-enriched target molecule, methods for calculating the dissociation constant of a ligand compound which binds to a 13C-enriched target molecule, and methods employed in the determination of the specific amino acids in a 13C-enriched target molecule affected by the binding of a ligand, as well as compounds identified by these screening methods, are provided herewith.

Abstract: The present invention provides a process for identifying compounds which bind to a specific target molecule. The process comprises the steps of: a) generating a first T.sub.2 - or diffusion-filtered proton spectrum of one or a mixture of chemical compounds; b) exposing one or a mixture of chemical compounds to the target molecule; c) generating a second T.sub.2 - or diffusion-filtered proton spectrum of one or a mixture of chemical compounds that has been exposed the target molecule in step (b); and d) comparing said first and second T.sub.2 - or diffusion-filtered proton spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.

Abstract: The present invention provides a process of designing compounds which bind to a specific target molecule. The process includes the steps of a) identifying a first ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; b) identifying a second ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; c) forming a ternary complex by binding the first and second ligands to the target molecule; d) determining the three dimensional structure of the ternary complex and thus the spatial orientation of the first and second ligands on the target molecule; and e) linking the first and second ligands to form the drug, wherein the spatial orientation of step (d) is maintained.

Abstract: The present invention provides a process of designing compounds which bind to a specific target molecule. The process includes the steps of a) identifying a first ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; b) identifying a second ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; c) forming a ternary complex by binding the first and second ligands to the target molecule; d) determining the three dimensional structure of the ternary complex and thus the spatial orientation of the first and second ligands on the target molecule; and e) linking the first and second ligands to form the drug, wherein the spatial orientation of step (d) is maintained.

Abstract: The present invention provides a process for identifying compounds which bind to a specific target molecule. The process includes the steps of a) generating a first two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of a .sup.15 N-labeled target molecule; b) exposing the labeled target molecule to one or a mixture of chemical compounds; c) generating a second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of the labeled target molecule that has been exposed to one or a mixture of compounds in step (b); and d) comparing said first and second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.

Abstract: The present invention provides a process for identifying compounds which bind to a specific target molecule. The process includes the steps of a) generating a first two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of a .sup.15 N-labeled target molecule; b) exposing the labeled target molecule to one or a mixture of chemical compounds; c) generating a second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of the labeled target molecule that has been exposed to one or a mixture of compounds in step (b); and d) comparing said first and second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.

Abstract: Compounds of formula ##STR1## or a pharmaceutically acceptable salt thereof inhibit matrix metalloproteinases and TNF.alpha. secretion and are useful in the treatment of inflammatory disease states. Also disclosed are matrix metalloproteinases and TNF.alpha. secretion inhibiting compositions and a method for inhibiting matrix metalloproteinases and TNF.alpha. secretion.