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Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Research Medicine, Veterans Affairs TVHS, Nashville, TN 37212, USA
* Author to whom correspondence should be addressed.
Received: 1 March 2011; in revised form: 25 March 2011 / Accepted: 29 March 2011 / Published: 1 April 2011
Abstract: In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.
Keywords: phenotypic screen; drug discovery; small molecules; drug design chemical genetics; model organisms
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MDPI and ACS Style
Williams, C.H.; Hong, C.C. Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery. Int. J. Mol. Sci. 2011, 12, 2262-2274.
Williams CH, Hong CC. Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery. International Journal of Molecular Sciences. 2011; 12(4):2262-2274.
Williams, Charles H.; Hong, Charles C. 2011. "Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery." Int. J. Mol. Sci. 12, no. 4: 2262-2274.