Title:Designed Multiple Ligands: Basic Research vs Clinical Outcomes
VOLUME: 19 ISSUE: 20
Author(s):L. Costantino and D. Barlocco
Affiliation:University of Modena e Reggio Emilia, Dipartimento di Scienze Farmaceutiche, Via Campi 183, 41100 Modena, Italy.
Keywords:Design strategy, drug coadministration, multifactorial pathologies, designed multiple ligands, multitarget compounds,
polypharmacology, neurodegenerative syndromes treatment, psychiatric disorders treatment, cardiovascular diseases treatment, diabetes
treatment, cancer treatment, anti-inflammatory compounds, antihistamines, antibacterials, antiparasitic
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.
