Human disease and drug pharmacology, complex as real life
| Autor: | Elisabet Viayna, O. Di Pietro, Diego Muñoz-Torrero, Irene Sola |
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| Přispěvatelé: | Universitat de Barcelona |
| Předmět: |
Drug
Farmacologia Phenotypic screening media_common.quotation_subject Context (language use) Disease Pharmacology Biochemistry Drug design Drug Discovery Medicine Animals Humans Molecular Targeted Therapy Protein Interaction Maps media_common Disseny de medicaments Interacció cel·lular Drug discovery business.industry Organic Chemistry Proteins Action (philosophy) Pharmaceutical Preparations Cell interaction Isolation (psychology) Molecular Medicine business Proteïnes Biological network |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | In the past decades drug discovery practice has escaped from the complexity of the formerly used phenotypic screening in animals to focus on assessing drug effects on isolated protein targets in the search for drugs that exclusively and potently hit one selected target, thought to be critical for a given disease, while not affecting at all any other target to avoid the occurrence of side-effects. However, reality does not conform to these expectations, and, conversely, this approach has been concurrent with increased attrition figures in late-stage clinical trials, precisely due to lack of efficacy and safety. In this context, a network biology perspective of human disease and treatment has burst into the drug discovery scenario to bring it back to the consideration of the complexity of living organisms and particularly of the (patho)physiological environment where protein targets are (mal)functioning and where drugs have to exert their restoring action. Under this perspective, it has been found that usually there is not one but several disease-causing genes and, therefore, not one but several relevant protein targets to be hit, which do not work on isolation but in a highly interconnected manner, and that most known drugs are inherently promiscuous. In this light, the rationale behind the currently prevailing single-target-based drug discovery approach might even seem a Utopia, while, conversely, the notion that the complexity of human disease must be tackled with complex polypharmacological therapeutic interventions constitutes a difficult-to-refuse argument that is spurring the development of multitarget therapies. |
| Databáze: | OpenAIRE |
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