Combinatorial Chemistry & High Throughput Screening - Volume 11, Issue 8, 2008

Chemogenomics is a recent scientific discipline that can be defined as the study of the interaction of functional biological systems with exogenous small molecules, or in broader sense the study of the intersection of biological and chemical spaces. This ambitious objective requires expertise in biology, chemistry and computational sciences (bioinformatics, cheminformatics, large scale statistics and machine learning methods) b Read More

Chemogenomics is the study of the interaction of functional biological systems with exogenous small molecules, or in broader sense the study of the intersection of biological and chemical spaces. Chemogenomics requires expertises in biology, chemistry and computational sciences (bioinformatics, cheminformatics, large scale statistics and machine learning methods) but it is more than the simple apposition of each Read More

Diversity-Oriented Synthesis (DOS) aims to broaden the frontier of accessible collections of complex and diverse small molecules. This review endeavours to dissect the DOS concept through three elements of diversity: building block, stereochemistry, and skeleton. Recent examples in the literature that emphasize the efficient combinations of these elements to generate diversity are reported.

The more recently discovered anthozoan fluorescent proteins (FPs) and the classic Aequorea victoria Green Fluorescent Protein (avGFP) as well as their derivatives have become versatile tools as live cell markers in fluorescence microscopy. In this review, we show the use of these FPs in drug discovery assays. Assay examples are given for the application of FPs in multiplexed imaging, as photosensitizers, as fluorescent timers, Read More

Cell-based screening using phenotypic assays is a useful means of identifying bioactive chemicals for use as tools to elucidate complex cellular processes. However, the chemicals must display sufficient selectivity and their targets have to be identified. We describe how cell-based screening assays can be designed to maximize the likelihood of discovering selective compounds through the choice of positive readouts, low che Read More

Microtubules are still a promising target for new therapeutic agents. Thus, there is a continuous interest for compounds able to modify microtubule assembly, either by interacting directly with tubulin, or by interacting with microtubules regulators. Because of its dynamic characteristics, the microtubule cytoskeleton is a suitable target for small molecules that rapidly diffuse in the cell cytoplasm. Moreover, compounds targeti Read More

Infectious diseases caused by protozoan parasites - malaria, sleeping sickness, leishmaniasis, Chagas' disease, toxoplasmosis - remain chronic problems for humanity. We lack vaccines and have limited drug options effective against protozoa. Research into anti-protozoan drugs has accelerated with improved in vitro cultivation methods, enhanced genetic accessibility, completed genome sequences for key protozoa, Read More

As plants lack a circulatory system and adaptive immune system, they have evolved their own defense systems distinct from animals, in which each plant cell is capable of defending itself from pathogens. Plants induce a number of defense responses, which are triggered by a variety of molecules derived from pathogenic microorganisms, referred to as microbe-associated molecular patterns (MAMPs), including peptides, Read More

Assignment of function to protein sequence is a task of growing importance in the life sciences, as new highthroughput sequencing DNA technologies generate ever increasing quantities of genomic and meta-genomic data. Patterns within the sequence space, caused by the evolutionary conservation and assembly of protein domains, make possible the inference of function from sequence similarity. Clusterin Read More

This article reviews the application of fragment descriptors at different stages of virtual screening: filtering, similarity search, and direct activity assessment using QSAR/QSPR models. Several case studies are considered. It is demonstrated that the power of fragment descriptors stems from their universality, very high computational efficiency, simplicity of interpretation and versatility.

The practical implementation and validation of a ligand-based approach to mining the chemogenomic space of drugs is presented and applied to the in silico target profiling of 767 drugs against 684 targets of therapeutic relevance. The results reveal that drugs targeting aminergic G protein-coupled receptors (GPCRs) show the most promiscuous pharmacological profiles. The detection of cross-pharmacologies between amin Read More

Support vector machines and kernel methods belong to the same class of machine learning algorithms that has recently become prominent in both computational biology and chemistry, although both fields have largely ignored each other. These methods are based on a sound mathematical and computationally efficient framework that implicitly embeds the data of interest, respectively proteins and small molecules, in high-di Read More

Dr. Eric Marechal is a CNRS Research Director, presently in charge of the Comparative Chemogenomics team at Institut de Recherches en Technologies et Sciences pour le Vivant, UMR 5168 CNRS-CEA-INRA-Universite J. Fourier, Grenoble, France. He received an Agregation teaching degree in Life Science (1990) from the Ministry of National Education, a MS (1991) in Cell Biology from Ecole Normale Supérieure de Lyo Read More