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Open access to anti-Trypanosomatid compounds selected from whole-cell high throughput screenings

Ana Rodriguez, Deputy Editor of PLOS NTDs, and Julio Alonso Padilla, former visiting fellow at GlaxoSmithKline, announce the disclosure of a large collection of antiparasitic compounds to facilitate research and drug development for Chagas Disease, Human African Trypanosomiasis (HAT) and Leishmaniasis.

trypanasome
Trypanosoma cruzi trypomastigote Image Credit: Carlos Bautista Ojeda http://www.carlosbautista.es

High throughput screening (HTS) against a particular microbe or target protein is a powerful tool for drug development against infectious diseases that Pharma companies frequently use. Three of the main Tropical Neglected Diseases –Chagas, HAT and Leishmaniasis– are in great need of new drugs with improved efficacy and lower toxicity, but the parasites causing these diseases are not frequently targeted outside academic labs. Recently, a Pharma company with the required facilities and experience in HTS, GlaxoSmithKline (GSK) merged forces with academic labs (New York University, University of Dundee and Instituto Lopez-Neyra of Granada) that were doing research in the parasites causing these diseases and screened a 1.8 million compound library against whole-cell Trypanosoma cruzi, Trypanosoma brucei and Leishmania donovani. As expected, these three large HTS have identified numerous compounds with activity against each of the parasites.

This valuable information has been processed at GSK to release 200 structures of compounds with activity against each parasite and is reported here. These compounds were selected with bioinformatics methodologies to include structures from different chemical families that are likely to be active against a wide variety of targets. The analysis suggests that most of the compounds are new chemical entities with potential novel mechanisms of actions that have not been previously clinically exploited against these parasites. Importantly, all the data have been made publicly available and the compound sets –called chemical boxes– will be provided on request as an open resource for researchers (contact julio.j.martin@gsk.com or albane.2.kessler@gsk.com).

Researchers in the field of drug development for trypanosomatid diseases have also an additional resource for testing more advanced candidate compounds. A service center which offers in vitro and mouse screening services for Trypanosoma cruzi, Trypanosoma brucei, Leishmania and Plasmodium is available to academic and pharma scientists. These resources should facilitate the early stages of development of new, improved medicines for trypanosomatid diseases.

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