The ‘Pathogen Box’


Last year I (Ryan West) attended the ISNTD-D3 2015 conference where I saw a presentation by Julio Martin from GSK Tres Cantos. He gave an interesting talk about open source drug discovery focusing on kinetoplastid diseases. One of the highlights of the talk for me was the introduction of three 200 compound collections that have been phenotypically identified as inhibitors of trypanosoma brucei, trypanosoma cruzi or leshmania donovani.

The collections were generated by screening a 1.8 million compound library from GSK against the pathogens in question. Hits were filtered to remove cytotoxic compounds and undesired structural features. The compound collections have been made available to public and private partners to facilitate research into neglected tropical diseases. Efficacy and cytotoxicity data has been published on ChEMBL and highlighted in Nature Scientific Reports 5: 8771 doi:10.138/srep08771.

Recently there has been a move towards encouraging and facilitating research into neglected tropical diseases. Medicines Malaria Venture (MMV) released a box of 400 compounds in 2011 that were active against the blood stage form of the P. falciparum parasite. Again, these compounds were freely available to the research community for further scientific investigation. This resulted in more than 40 publications, the depositing of publicly accessible data from over 20 screens and the initiation of at least 3 medicinal chemistry programs for a range of neglected tropical diseases.

Continuing from the success of the ‘Malaria Box’ initiative MMV have been awarded a further grant from the Bill and Melinda Gates foundation to collate another library of compounds. This time the molecules have been identified phenotypically against a broader range of 8 unique pathogens which are responsible for a large proportion of the world’s neglected tropical diseases. The collection has been available from December 2015, and as part of my project I have been able to acquire one of the kits for testing. We are interested in an enzyme target responsible for the blood stream respiration of the parasite that causes human African trypanosomiasis. We hope to publish our results in the near future.

This open source approach of sharing compound collections along with generated experimental data will boost research and aid the discovery of novel molecules for treating neglected tropical diseases. It will be interesting to see the progress of these open source endeavours and if they will be more widely adopted by other disease areas.

 

Blog written by Ryan West

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