Combinatorial Chemistry & High Throughput Screening - Volume 12, Issue 10, 2009

The Human Genome Project [1] identified approximately 30,000 genes and subsequent to the completion of this project a subset of these genes, approximately 3,000-10,000, have been identified as critical in the pathogenesis of disease [2, 3]. In a comprehensive review of pharmaceutical industry portfolios Drews and colleagues suggested that there are approximately 500 drug targets currently, but they proposed that the Read More

Cyclic peptides have been often utilized as metabolically stable, conformationally restricted mimics of different kinds of biologically active peptides, including peptide antibiotics, endogenous opioid peptides, integrin inhibitors, peptide hormones, anticancer peptides, and so on. And in particular, cyclic compounds which can mimic important secondary structure elements such as β-turns are of outstanding importance. Since great Read More

Advances in protein modeling algorithms and state-of-the-art sequence similarity comparison and fold recognition methods, in combination with growing protein structure information, are facilitating “genome-to-drug lead” approaches in which chemicals are virtually screened against computationally-predicted protein targets. Although the quality of predicted protein structures by homology modeling methods, and thu Read More

Urokinase receptor (uPAR) is a widely recognized target for potential treatment of cancer. The development of uPAR inhibitors has been going on for over a decade. Despite the identification and validation of many highly potent hits using screening or medicinal approaches, none of them has been moved further along the drug discovery pipeline. The development of uPAR inhibitors exemplifies several challenges now faced by Read More

Low molecular weight inhibitors of Protein-Protein Interactions (PPI's) have been identified for a number of different systems indicating the viability of the computer-aided drug design approaches. However, pathways undertaken by researchers in pharmaceutical companies or in academic laboratories are not always clearly defined and the protocols that allow the identification of lead compounds often remain blurry. We will Read More

Recent advances in combinatorial chemistry (CC) and High throughput screening (HTS) approaches for use in drug discovery have made it possible to synthesize and/or screen large repositories of chemically diverse scaffolds in search of small molecules that disrupt or regulate macromolecular function. Although successful in the discovery of novel therapeutics this approach is both costly and time consuming. In silico computer Read More

Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. In this review, we first introduce structure-based virtual ligand screening and briefly comment on compound collections and target preparations. We also provide the readers with a list of resources, from chemoinfo Read More

Alan Rigby is currently an Assistant Professor of Medicine at Harvard Medical School and the Interim Director of the Drug Discovery and Target Validation Program in the Center for Vascular Biology at Beth Israel Deaconess Medical Center. His laboratory is located in the Center for Vascular Biology Research, the Division of Molecular and Vascular Medicine in the Department of Medicine at Beth Israel Deaconess Medical Cent Read More