Improving the efficacy-safety balance of polypharmacology in multi-target drug discovery.
Expert Opin Drug Discov
; 13(2): 179-192, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-29233023
ABSTRACT
INTRODUCTION:
Polypharmacology has emerged as an essential paradigm for modern drug discovery process. Multiple lines of evidence suggest that agents capable of modulating multiple targets in a selective manner may offer also improved balance between therapeutic efficacy and safety compared to single-targeted agents. Areas covered Herein, the authors review the recent progress made in experimental and computational strategies for addressing the critical challenges with rational discovery of selective multi-targeted agents within the context of polypharmacological modelling. Specific focus is placed on multi-targeted mono-therapies, although examples of combinatorial polytherapies are also covered as an important part of the polypharmacology paradigm. The authors focus mainly on anti-cancer treatment applications, where polypharmacology is playing a key role in determining the efficacy-toxicity trade-off of multi-targeting strategies. Expert opinion Even though it is widely appreciated that complex polypharmacological interactions can contribute both to therapeutic and adverse side-effects, systematic approaches for improving this balance by means of integrated experimental-computational strategies are still lacking. Future developments will be needed for comprehensive collection and harmonization of systems-wide target selectivity data, enabling better utilization and control for multi-targeted activities in the drug development process. Additional areas of future developments include model-based strategies for drug combination screening and improved pre-clinical validation options with animal models.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Descubrimiento de Drogas
/
Polifarmacología
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Discov
Año:
2018
Tipo del documento:
Article
País de afiliación:
Finlandia