Showing papers on "Chemical library published in 2006"

Latest development in drug discovery on G protein-coupled receptors.

Abstract: G protein-coupled receptors (GPCRs) represent the family of proteins with the highest impact from social, therapeutic and economic point of view. Today, more than 50% of drug targets are based on GPCRs and the annual worldwide sales exceeds 50 billion dollars. GPCRs are involved in all major disease areas such as cardiovascular, metabolic, neurodegenerative, psychiatric, cancer and infectious diseases. The classical drug discovery process has relied on screening compounds, which interact favorably with the GPCR of interest followed by further chemical engineering as a mean of improving efficacy and selectivity. In this review, methods for sophisticated chemical library screening procedures will be presented. Furthermore, development of cell-based assays for functional coupling of GPCRs to G proteins will be discussed. Finally, the possibility of applying structure-based drug design will be summarized. This includes the application of bioinformatics knowledge and molecular modeling approaches in drug development programs. The major efforts established through large networks of structural genomics on GPCRs, where recombinantly expressed GPCRs are subjected to purification and crystallization attempts with the intention of obtaining high-resolution structures, are presented as a promising future approach for tailor-made drug development.

Small molecule inhibitors of hiv-1 capsid assembly

Abstract: The present invention provides novel methods of treating HIV infections employing small molecule inhibitors identified by chemical library (DIVERSet™ library). These small molecule inhibitors may specifically bind to HIV-1 capsid protein thereby interfering with capsid assembly. The small molecule inhibitors of the present invention can be potential drug targets in the treatment of HIV infection.

Design and characterization of a functional library for NMR screening against novel protein targets.

Abstract: In the past few years, NMR has been extensively utilized as a screening tool for drug discovery using various types of compound libraries. The designs of NMR specific chemical libraries that utilize a fragment-based approach based on drug-like characteristics have been previously reported. In this article, a new type of compound library will be described that focuses on aiding in the functional annotation of novel proteins that have been identified from various ongoing genomics efforts. The NMR functional chemical library is comprised of small molecules with known biological activity such as: co-factors, inhibitors, metabolites and substrates. This functional library was developed through an extensive manual effort of mining several databases based on known ligand interactions with protein systems. In order to increase the efficiency of screening the NMR functional library, the compounds are screened as mixtures of 3-4 compounds that avoids the need to deconvolute positive hits by maintaining a unique NMR resonance and function for each compound in the mixture. The functional library has been used in the identification of general biological function of hypothetical proteins identified from the Protein Structure Initiative.

Alpha-helix mimetics and methods relating to the treatment of fibrotic disorders

Abstract: The invention provides α-mimetic structures and a chemical library relating thereto. Additionally, the invention provides methods wherein α-mimetic compounds are used to treat fibrotic disorders.

In silico Identification of Novel EGFR Inhibitors with Antiproliferative Activity Against Cancer Cells.

Abstract: Inhibition of the epidermal growth factor receptor (EGFR) tyrosine kinase activity by small molecules has proved effective for the treatment of cancer. To the best of our knowledge, the crystal structure of EGFR has been used for the first time to identify novel inhibitor chemotypes by docking-based in silico screening of a large virtual chemical library followed up by experimental validation. We identified several compounds with antiproliferative effects on cancer cells. Amongst them, a C(4)-N(1)-substituted pyrazolo[3,4-d]pyrimidine MSK-039 (39) was discovered as a low-micromolar inhibitor of EGFR tyrosine kinase activity. The predicted binding mode of 39 opens a new avenue toward the optimization of novel chemical entities to develop potent and selective inhibitors of EGFR signaling.