Hit Triage and Validation in Phenotypic Screening: Considerations and Strategies.

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 Biol

journal_title

Cell chemical biology

authors

Vincent F,Loria PM,Weston AD,Steppan CM,Doyonnas R,Wang YM,Rockwell KL,Peakman MC

doi

10.1016/j.chembiol.2020.08.009

subject

Has Abstract

pub_date

2020-11-19 00:00:00

pages

1332-1346

issue

11

eissn

2451-9456

issn

2451-9448

pii

S2451-9456(20)30331-7

journal_volume

27

pub_type

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