Hit Triage and Validation in Phenotypic Screening: Considerations and Strategies.
| Autor: | Vincent F; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA. Electronic address: fabien.vincent@pfizer.com., Loria PM; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA., Weston AD; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA., Steppan CM; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA., Doyonnas R; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA., Wang YM; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA., Rockwell KL; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA., Peakman MC; Discovery Sciences, Pfizer, 445 Eastern Point Road, Groton, CT 06340, USA. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Cell chemical biology [Cell Chem Biol] 2020 Nov 19; Vol. 27 (11), pp. 1332-1346. Date of Electronic Publication: 2020 Sep 03. |
| DOI: | 10.1016/j.chembiol.2020.08.009 |
| Abstrakt: | 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. Competing Interests: Declaration of Interests F.V., P.M.L., A.D.W., C.M.S., R.D., Y.-M.W., K.L.R., and M.-C.P. are employees of Pfizer, Inc. (Copyright © 2020 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|