Drug discovery programs sponsored by public or private initiatives pursue the same ambitious goal: a crushing defeat of major Neglected Tropical Diseases (NTDs) during this decade. Both target-based and target-free screenings have pros and cons when it comes to finding potential small-molecule leads among chemical libraries consisting of myriads of compounds. Within the target-based strategy, crystals of pathogen recombinant-proteins are being used to obtain three-dimensional (3D) structures in silico for the discovery of structure-based inhibitors. On the other hand, genetically modified parasites expressing easily detectable reporters are in the pipeline of target-free (phenotypic) screenings. Furthermore, lead compounds can be scaled up to in vivo preclinical trials using rodent models of infection monitoring parasite loads by means of cutting-edge bioimaging devices. As such, those preferred are fluorescent and bioluminescent readouts due to their reproducibility and rapidity, which reduces the number of animals used in the trials and allows for an earlier stage detection of the infective process as compared with classical methods. In this review, we focus on the current differences between target-based and phenotypic screenings in Leishmania, as an approach that leads to the discovery of new potential drugs against leishmaniasis.

Target-based vs. phenotypic screenings in Leishmania drug discovery: A marriage of convenience or a dialogue of the deaf? / R.M. Reguera, E. Calvo-Alvarez, R. Alvarez-Velilla, R. Balaña-Fouce. - In: INTERNATIONAL JOURNAL FOR PARASITOLOGY, DRUGS AND DRUG RESISTANCE. - ISSN 2211-3207. - 4:3(2014 Dec), pp. 355-357. [10.1016/j.ijpddr.2014.05.001]

Target-based vs. phenotypic screenings in Leishmania drug discovery: A marriage of convenience or a dialogue of the deaf?

E. Calvo-Alvarez
Secondo
;
2014

Abstract

Drug discovery programs sponsored by public or private initiatives pursue the same ambitious goal: a crushing defeat of major Neglected Tropical Diseases (NTDs) during this decade. Both target-based and target-free screenings have pros and cons when it comes to finding potential small-molecule leads among chemical libraries consisting of myriads of compounds. Within the target-based strategy, crystals of pathogen recombinant-proteins are being used to obtain three-dimensional (3D) structures in silico for the discovery of structure-based inhibitors. On the other hand, genetically modified parasites expressing easily detectable reporters are in the pipeline of target-free (phenotypic) screenings. Furthermore, lead compounds can be scaled up to in vivo preclinical trials using rodent models of infection monitoring parasite loads by means of cutting-edge bioimaging devices. As such, those preferred are fluorescent and bioluminescent readouts due to their reproducibility and rapidity, which reduces the number of animals used in the trials and allows for an earlier stage detection of the infective process as compared with classical methods. In this review, we focus on the current differences between target-based and phenotypic screenings in Leishmania, as an approach that leads to the discovery of new potential drugs against leishmaniasis.
Drug discovery; HCS, High Content Screening; HTS, high throughput screening; Leishmania; NTD, Neglected Tropical Diseases; Phenotypic HTS; TDR, Special Programme for Research and Training in Tropical Diseases; Target HTS
Settore MED/04 - Patologia Generale
dic-2014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/971381
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