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Novel paradigms for drug discovery: computational multitarget screening
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Document Title
Novel paradigms for drug discovery: computational multitarget screening
Author
Jenwitheesuk E, Horst JA, Rivas KL, Van Voorhis WC, Samudrala R
Name from Authors Collection
Affiliations
University of Washington; University of Washington Seattle; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
Type
Review
Source Title
TRENDS IN PHARMACOLOGICAL SCIENCES
ISSN
0165-6147
Year
2008
Volume
29
Open Access
Green Accepted
Publisher
ELSEVIER SCIENCE LONDON
DOI
10.1016/j.tips.2007.11.007
Format
Abstract
An established paradigm in current drug development is (i) to identify a single protein target whose inhibition is likely to result in the successful treatment of a disease of interest; (ii) to assay experimentally large libraries of small-molecule compounds in vitro and in vivo to identify promising inhibitors in model systems; and (iii) to determine whether the findings are extensible to humans. This complex process, which is largely based on trial and error, is risk-, time- and cost-intensive. Computational (virtual) screening of drug-like compounds simultaneously against the atomic structures of multiple protein targets, taking into account protein-inhibitor dynamics, might help to identify lead inhibitors more efficiently, particularly for complex drug-resistant diseases. Here we discuss the potential benefits of this approach, using HIV-1 and Plasmodium falciparum infections as examples. We propose a virtual drug discovery 'pipeline' that will not only identify lead inhibitors efficiently, but also help minimize side-effects and toxicity, thereby increasing the likelihood of successful therapies.
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Funding Sponsor
NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [F30DE017522] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R33GM068152] Funding Source: NIH RePORTER; NIDCR NIH HHS [F30 DE017522, F30DE017522, F30 DE017522-02] Funding Source: Medline; NIGMS NIH HHS [GM068152, R33 GM068152] Funding Source: Medline
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WOS