Journal
CURRENT OPINION IN CHEMICAL BIOLOGY
Volume 13, Issue 5-6, Pages 549-555Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.cbpa.2009.08.003
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Funding
- Canadian Institutes of Health Research [R01CA097061]
- NIH [R01CA097061, R01GM085081]
- Arnold and Mabel Beckman Foundation
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Many disease genes encode proteins that are difficult to target directly using small molecule drugs. Improvements in libraries based on synthetic compounds, natural products, and other types of molecules may ultimately allow some challenging proteins to be successfully targeted; however, these developments alone are unlikely to be sufficient. A complementary strategy exploits the functional interconnectivity of intracellular networks to find druggable targets lying upstream, downstream, or in parallel to a disease-causing gene, where modulation can influence the disease process indirectly. These targets can be selected using prior knowledge of disease-associated pathways or identified using phenotypic chemical and genetic screens in model organisms and cells. These approaches should facilitate the identification of effective drug targets for many genetic disorders.
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