Abstract:
: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.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Vincent F,Loria PM,Weston AD,Steppan CM,Doyonnas R,Wang YM,Rockwell KL,Peakman MCdoi
10.1016/j.chembiol.2020.08.009subject
Has Abstractpub_date
2020-11-19 00:00:00pages
1332-1346issue
11eissn
2451-9456issn
2451-9448pii
S2451-9456(20)30331-7journal_volume
27pub_type
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