The clinical treatment of multifactorial pathologies (e.g. cancer, Alzheimer's disease, psychiatric disorders), is still a major challenge. Many researches have been published dealing with the design of multiple ligands, able to act at the same time towards several targets relevant for a given pathology. In the present review, the clinical results about these compounds have been reported, together with the design strategy adopted, in order to allow a critical evaluation of the outcomes of these efforts. What is emerging is that several effective design strategies of multitarget compounds are available, and the choice among these appears to be dependent on the therapeutic area considered. However, at present, besides multitarget drugs discovered during optimization efforts by means of phenotypic assays, drug coadministrations or fixed dose formulations appear to be more useful therapeutic options than designed multiple ligands; this scenario will change when systems biology will be able to select critical targets, i.e. nodal proteins that should be inhibited in order to obtain a therapeutic action; at this point, the design of multiple ligands will allow a renaissance of medicinal chemistry.

Designed multiple ligands: basic research vs clinical outcomes / L. Costantino, D. Barlocco. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - 19:20(2012), pp. 3353-3387. [10.2174/092986712801215883]

Designed multiple ligands: basic research vs clinical outcomes

D. Barlocco
Ultimo
2012

Abstract

The clinical treatment of multifactorial pathologies (e.g. cancer, Alzheimer's disease, psychiatric disorders), is still a major challenge. Many researches have been published dealing with the design of multiple ligands, able to act at the same time towards several targets relevant for a given pathology. In the present review, the clinical results about these compounds have been reported, together with the design strategy adopted, in order to allow a critical evaluation of the outcomes of these efforts. What is emerging is that several effective design strategies of multitarget compounds are available, and the choice among these appears to be dependent on the therapeutic area considered. However, at present, besides multitarget drugs discovered during optimization efforts by means of phenotypic assays, drug coadministrations or fixed dose formulations appear to be more useful therapeutic options than designed multiple ligands; this scenario will change when systems biology will be able to select critical targets, i.e. nodal proteins that should be inhibited in order to obtain a therapeutic action; at this point, the design of multiple ligands will allow a renaissance of medicinal chemistry.
Anti-inflammatory compounds; Antibacterials; Antihistamines; Antiparasitic; Cancer treatment; Cardiovascular diseases treatment; Design strategy; Designed multiple ligands; Diabetes treatment; Drug coadministration; Multifactorial pathologies; Multitarget compounds; Neurodegenerative syndromes treatment; Polypharmacology; Psychiatric disorders treatment
Settore CHIM/08 - Chimica Farmaceutica
2012
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/203421
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