Dataset Information

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles.

ABSTRACT: The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.

SUBMITTER: Williamson AE

PROVIDER: S-EPMC5084075 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles.

Williamson Alice E AE Ylioja Paul M PM Robertson Murray N MN Antonova-Koch Yevgeniya Y Avery Vicky V Baell Jonathan B JB Batchu Harikrishna H Batra Sanjay S Burrows Jeremy N JN Bhattacharyya Soumya S Calderon Felix F Charman Susan A SA Clark Julie J Crespo Benigno B Dean Matin M Debbert Stefan L SL Delves Michael M Dennis Adelaide S M AS Deroose Frederik F Duffy Sandra S Fletcher Sabine S Giaever Guri G Hallyburton Irene I Gamo Francisco-Javier FJ Gebbia Marinella M Guy R Kiplin RK Hungerford Zoe Z Kirk Kiaran K Lafuente-Monasterio Maria J MJ Lee Anna A Meister Stephan S Nislow Corey C Overington John P JP Papadatos George G Patiny Luc L Pham James J Ralph Stuart A SA Ruecker Andrea A Ryan Eileen E Southan Christopher C Srivastava Kumkum K Swain Chris C Tarnowski Matthew J MJ Thomson Patrick P Turner Peter P Wallace Iain M IM Wells Timothy N C TN White Karen K White Laura L Willis Paul P Winzeler Elizabeth A EA Wittlin Sergio S Todd Matthew H MH

ACS central science 20160914 10

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ...[more]

PMID: 27800551

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Project description:BackgroundOpen source drug discovery offers potential for developing new and inexpensive drugs to combat diseases that disproportionally affect the poor. The concept borrows two principle aspects from open source computing (i.e., collaboration and open access) and applies them to pharmaceutical innovation. By opening a project to external contributors, its research capacity may increase significantly. To date there are only a handful of open source R&D projects focusing on neglected diseases. We wanted to learn from these first movers, their successes and failures, in order to generate a better understanding of how a much-discussed theoretical concept works in practice and may be implemented.Methodology/principal findingsA descriptive case study was performed, evaluating two specific R&D projects focused on neglected diseases. CSIR Team India Consortium's Open Source Drug Discovery project (CSIR OSDD) and The Synaptic Leap's Schistosomiasis project (TSLS). Data were gathered from four sources: interviews of participating members (n = 14), a survey of potential members (n = 61), an analysis of the websites and a literature review. Both cases have made significant achievements; however, they have done so in very different ways. CSIR OSDD encourages international collaboration, but its process facilitates contributions from mostly Indian researchers and students. Its processes are formal with each task being reviewed by a mentor (almost always offline) before a result is made public. TSLS, on the other hand, has attracted contributors internationally, albeit significantly fewer than CSIR OSDD. Both have obtained funding used to pay for access to facilities, physical resources and, at times, labor costs. TSLS releases its results into the public domain, whereas CSIR OSDD asserts ownership over its results.Conclusions/significanceTechnically TSLS is an open source project, whereas CSIR OSDD is a crowdsourced project. However, both have enabled high quality research at low cost. The critical success factors appear to be clearly defined entry points, transparency and funding to cover core material costs.

Dataset Information

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles.

Publications

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles.

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