Drugs exert their therapeutic effect by binding and regulating the activity of a particular protein or nucleic acid target. A large number of targets have been explored for drug discovery. Continuous ...effort has been directed at the search for new targets and more-extensive exploration of existing targets. Knowledge of these targets facilitates the understanding of molecular mechanisms of drugs and the effort required for drug discovery and target searches. Areas of progress, current focuses of research and development and the difficulties in target exploration are reviewed. The characteristics of the currently explored targets and their correlation to the level of difficulty for target exploration are analyzed. From these characteristics, simple rules can be derived for estimating the difficulty level of target exploration. The feasibility of predicting druggable proteins by using simple rules and sequence-derived physicochemical properties is also discussed.
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22.
Deformylase as a novel antibacterial target Yuan, Zhengyu; Trias, Joaquim; White, Richard J
Drug Discovery Today,
09/2001, Volume:
6, Issue:
18
Book Review, Journal Article
Peer reviewed
Bacterial genomics has revealed a plethora of previously unknown targets of potential use in the discovery of novel antibacterial drugs. However, so far little has emerged from this approach. Peptide ...deformylase is an interesting target that was discovered more than 30 years ago, but was not exploited until recently. The reawakening of interest in this target resulted from an improved understanding of the enzyme, making it a more tractable and attractive target. Information on the properties of the enzyme, such as its three-dimensional structure, the activity of inhibitors, its resistance and suitability as a target are discussed.
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Tyrosine kinases are important therapeutic targets in drug discovery high-throughput screening programs. Homogeneous time-resolved fluorescence (HTRF) eliminates many of the problems associated with ...some conventional screening assay methodologies and this has made the development of tyrosine kinase HTRF assays an exciting prospect for pharmaceutical companies. The authors illustrate the utility of this technology in the light of experience within five pharmaceutical companies.
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An alternative approach to miniaturization has been developed that does not rely upon increasing microtiter plate densities. Gel-permeation assays, originally developed for screening antibody–antigen ...interactions and anti-microbial screening, are a well-less technique. Newer approaches extending this technology to enable the screening of traditional compound-collections show exceptional promise and offer the potential to convert most (if not all) 96-well assays into this novel high-density format.
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A new class of kinase-related drug targets with the promise of novel therapies for inflammation, cancer, and infectious diseases.
Posttranslational modifications of proteins such as phosphorylation ...have been recognized as pivotal modulators of biological activity in healthy and diseased tissues. Sulfation is a key posttranslational modification the role of which in physiology and pathology is only now becoming appreciated. Whereas phosphorylation is central to intracellular signal transduction, sulfation modulates cell-cell and cell-matrix communication. Sulfation involves a class of enzymes known as sulfotransferases, which transfer sulfate from the ATP-like sulfate donor 3′phosphoadenosine-5′phosphosulate to glycoproteins, glycolipids or metabolites. This review focuses on Golgi-localized sulfotransferases, their molecular biology and biochemistry, and strategies towards discovery of sulfotransferase inhibitors that could have potential as therapeutics in inflammation, cancer and infectious diseases.
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