Tse, EG;
Aithani, L;
Anderson, M;
Cardoso-Silva, J;
Cincilla, G;
Conduit, GJ;
Galushka, M;
... Todd, MH; + view all
(2021)
An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials.
Journal of Medicinal Chemistry
10.1021/acs.jmedchem.1c00313.
(In press).
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Abstract
The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as "ill-advised". Since all data and participant interactions remain in the public domain, this research project "lives" and may be improved by others.
| Type: | Article |
|---|---|
| Title: | An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.jmedchem.1c00313 |
| Publisher version: | https://doi.org/10.1021/acs.jmedchem.1c00313 |
| Language: | English |
| Additional information: | © 2021 The Authors. Published by American Chemical Society. This is an open access article under the CC BY 4.0 license Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10138986 |
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