The future of phenotypic drug discovery.
Cell Chem Biol
; 28(3): 424-430, 2021 03 18.
Article
en En
| MEDLINE
| ID: mdl-33529582
Phenotypic drug discovery (PDD) uses biological systems directly for new drug screening. While PDD has proved effective in the discovery of drugs with novel mechanisms, for broader adoption, key challenges need resolution: progression of poorly qualified leads and overloaded pipelines due to lack of effective tools to process and prioritize hits; and advancement of leads with undesirable mechanisms that fail at more expensive stages of discovery. Here I discuss how human-based phenotypic platforms are being applied throughout the discovery process for hit triage and prioritization, for elimination of hits with unsuitable mechanisms, and for supporting clinical strategies through pathway-based decision frameworks. Harnessing the data generated in these platforms can also fuel a deeper understanding of drug efficacy and toxicity mechanisms. As these approaches increase in use, they will gain in power for driving better decisions, generating better leads faster and in turn promoting greater adoption of PDD.
Palabras clave
Microphysiological systems; Phenotypic assay; adverse outcome pathway; assay performance; assay qualification; cell-based assays; discovery program outcome pathway; drug discovery; drug discovery innovation; drug discovery productivity; drug safety; drug screening; hit prioritization; hit triage; human cells; lead discovery; mechanism of action; non-animal alternatives; phenotypic drug discovery; phenotypic profiling; primary cells; translational research
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Descubrimiento de Drogas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Estados Unidos