Diversity & tractability revisited in collaborative small molecule phenotypic screening library design.
Bioorg Med Chem
; 28(1): 115192, 2020 01 01.
Article
en En
| MEDLINE
| ID: mdl-31837897
ABSTRACT
Identification of purposeful chemical matter on a broad range of drug targets is of high importance to the pharmaceutical industry. However, disease-relevant but more complex hit-finding plans require flexibility regarding the subset of the compounds that we screen. Herein we describe a strategy to design high-quality small molecule screening subsets of two different sizes to cope with a rapidly changing early discovery portfolio. The approach taken balances chemical tractability, chemical diversity and biological target coverage. Furthermore, using surveys, we actively involved chemists within our company in the selection process of the diversity decks to ensure current medicinal chemistry principles were incorporated. The chemist surveys revealed that not all published PAINS substructure alerts are considered productive by the medicinal chemistry community and in agreement with previously published results from other institutions, QED scores tracked quite well with chemists' notions of chemical attractiveness.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Bibliotecas de Moléculas Pequeñas
/
Descubrimiento de Drogas
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos