期刊
ACS INFECTIOUS DISEASES
卷 4, 期 3, 页码 301-314出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.7b00276
关键词
malaria; phenotypic screening; selections; resistance
资金
- NIH [5R01AI090141, R01AI103058]
- Bill and Melinda Gates Foundations [OPP1086217, OPP1141300]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI090141, R01AI103058] Funding Source: NIH RePORTER
Although many new anti-infectives have been discovered and developed solely using phenotypic cellular screening and assay optimization, most researchers recognize that structure-guided drug design is more practical and less costly. In addition, a greater chemical space can be interrogated with structure-guided drug design. The practicality of structure-guided drug design has launched a search for the targets of compounds discovered in phenotypic screens. One method that has been used extensively in malaria parasites for target discovery and chemical validation is in vitro evolution and whole genome analysis (IVIEWGA). Here, small molecules from phenotypic screens with demonstrated antiparasitic activity are used in genome-based target discovery methods. In this Review, we discuss the newest, most promising druggable targets discovered or further validated by evolution-based methods, as well as some exceptions.
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