期刊
CELL CHEMICAL BIOLOGY
卷 27, 期 11, 页码 1332-1346出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2020.08.009
关键词
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The promise of phenotypic screening resides in its track record of novel biology and first-in-class therapies. However, challenges stemming from major differences between target-based and phenotypic screening do exist. These challenges prompted us to rethink the critical stage of hit triage and validation on the road to clinical candidates and novel drug targets. Whereas this process is usually straightforward for target screening hits, phenotypic screening hits act through a variety of mostly unknown mechanisms within a large and poorly understood biological space. Our analysis suggests successful hit triage and validation is enabled by three types of biological knowledge-known mechanisms, disease biology, and safety-while structure-based hit triage may be counterproductive.
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