Systematic Assessment of Fragment Identification for Multitarget Drug Design.
ChemMedChem
; 16(7): 1088-1092, 2021 04 08.
Article
en En
| MEDLINE
| ID: mdl-33283450
ABSTRACT
Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment library for comprehensive screening on five targets chosen from proteins for which multitarget ligands have been successfully developed previously (soluble epoxide hydrolase, leukotriene A4 hydrolase, 5-lipoxygenase, retinoid X receptor, farnesoid X receptor). Differential scanning fluorimetry served as primary screening method before fragments hitting at least two targets were validated in orthogonal assays. Thereby, we obtained valuable fragment leads with dual-target engagement for six out of ten target combinations. Our results demonstrate the applicability of fragment-based approaches to identify starting points for polypharmacological compound development with certain limitations.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Inhibidores Enzimáticos
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania