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Can Binding Kinetics Translate to a Clinically Differentiated Drug? From Theory to Practice

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Most drugs initiate their effects by binding to a drug target. The kinetics of binding have the potential to influence the utility of a drug. Physiology uses the magnitude of kinetic barriers to differentiate between reversible and irreversible states, leading to differentiated phenotypes. Under the appropriate circumstances the therapeutic index of some drugs is influenced by the kinetics and reversibility of a system. The ability for differentiated binding kinetics to define irreversible or reversible states and the impact of these differentiated states on a clinical outcome is proposed here to contribute to the magnitude of gastrointestinal toxicity observed with nonsteroidal anti-inflammatory agents (NSAIDs). This example and others highlight the potential for differentiated binding kinetics to provide clinical differentiation.





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Keywords: Cyclooxygenase; GI toxicity; Irreversible; Kinetics; NSAID; Pharmacology

Document Type: Research Article

Affiliations: Roche Palo Alto, m/s R2-101, 3431 Hillview Ave, Palo Alto, CA 94304, USA.

Publication date: 01 October 2006

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  • Letters in Drug Design & Discovery publishes original letters on all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of Internet technology for both the submission and review of manuscripts. The journal is essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
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