Abstract: Isoform-selective lysine deacetylase inhibitors are described. Inhibitors of the lysine deacetylase enzyme are useful as antitumor drugs and for treating addiction, asthma, cardio-vascular disease, immunosuppression, neurodegenerative diseases, sepsis, sickle-cell disease, uveal melanoma and termination of viral latency, particularly HIV-1 latency.

Abstract: Methods of using KDAC inhibitor compounds for the treatment of various parasitic diseases are described.

Abstract: Isoform-selective lysine deacetylase inhibitors are described. Inhibitors of the lysine deacetylase enzyme are useful as antitumor drugs and for treating addiction, asthma, cardio-vascular disease, immunosuppression, neurodegenerative diseases, sepsis, sickle-cell disease, uveal melanoma and termination of viral latency, particularly HIV-1 latency.

Abstract: Methods of using KDAC inhibitor compounds for the treatment of various parasitic diseases are described.

Abstract: The present invention provides, inter alia, methods, models, and systems for selecting an effector having specificity for a target molecule. The methods and systems of the present invention involve several steps, including compiling a database containing structural data for a library of molecules and a population of ligands and activity data, establishing structure-based equivalence of sequence elements in the library of molecules, determining likely spatial orientations of population ligands in library molecules, calculating interaction energies for each ligand-molecule pair, generating statistical models that are predictive of sequence elements likely to contribute to a differential effect of ligands on molecules, selecting an effector that is likely to have a desired specificity for the target molecule, experimentally determining activity data for effector-library molecule pairs, and at least once repeating the steps listed above wherein the effector is a member of the population of ligands.

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

Abstract: The present invention is directed to the making of library of conformationally constrained peptides and peptidomimetics including chiral azacrowns for use as conformational templates when complexed with metals for the production of conformationally constrained bioactive peptides for use in elucidation of the binding sites and functional groups on the receptor/peptide ternary complex.

Abstract: Novel inhibitors of retroviral protease, e.g., HIV protease, are provided which are peptides having from about 4 to about 8 amino acid residues and which are substrates for said protease derived from known cleavage sites and modified to contain an internal CH.sub.2 NH bond isostere.

Abstract: Novel inhibitors of retroviral protease, e.g., HIV protease, are provided which are peptides having from about 4 to about 8 amino acid residues and which are substrates for said protease derived from known cleavage sites and modified to contain an internal CH.sub.2 NH bond isostere.

Abstract: Novel fluorogenic substrates for retroviral protease, e.g. HIV protease, having the chemical structure X-Thr-Ile-Nle-Phe(Y)-Gln-Arg-NH.sub.2 wherein X is a fluorogenic group and Y is an acceptor for the fluorogenic group, and their use in a fluorometric method for the determination of retroviral protease is disclosed.

Abstract: Disclosed herein are compounds of the class of peptides having from about 4 to about 8 amino acid residues that are substrates for retroviral protease, e.g., HIV protease, derived from known cleavage sites and that are modified to contain an internal COCH.sub.2 bond isostere, useful as inhibitors of said retroviral protease, e.g., HIV protease, and exemplified by the modified peptide, Abz-Thr-Ile-Nle.PSI.(K)Nle-Gln-Arg-NH.sub.2, wherein K is COCH.sub.2.

Abstract: Novel fluorogenic substrates for retroviral protease, e.g. HIV protease, having the chemical structure X--Thr--Ile--Nle--Phe(Y)--Gln--Arg--NH.sub.2 wherein X is a fluorogenic group and Y is an acceptor for the fluorogenic group, and their use in a fluorometric method for the determination of retroviral protease is disclosed.

Abstract: Vasopressin-like peptide whose structures have been modified by an alpha-methyl amino acid at the 4 or 7 position are set forth. These compounds have potent vasopressin antagonist activities.

Abstract: Peptides having vasopressin antagonist activity are prepared by a peptide synthesizer to insert a N-methylarginine at the 7-position of the structure. An example of this series of compounds is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl-D-tyrosine)-4-valine-7-desproline-8-N-methylarginine-9-de sglycine]-vasopressin.