New published paper: Antimalarial drug discovery Optibrium and OSM.
Nov 2021. Now published in the Journal of Medicinal Chemistry – Alchemite™ machine learning applied to antimalarial drug discovery.
“Congratulations to the Optibrium/Intellegens team for contributing one of the best models, using Alchemite. We’re excited by the new molecules that were suggested because they are not ones that we would necessarily have thought of ourselves.”
– Dr Matthew Todd, Professor of Drug Discovery at UCL School of Pharmacy and founder of the OSM.
Key outcomes
Intellegens and drug discovery partner Optibrium contributed to the Open Source Malaria project.
- Alchemite™ machine learning predicted a new antimalarial compound which showed good potency when synthesised and tested.
- The study outperformed alternative approaches, succeeding despite the sparsity of available experimental bioactivity data.
- Alchemite™ opened up new possibilities – the compound identified would have been dismissed as a candidate by the chemists assessing the project.
Summary
Malaria is a parasitic infection transmitted by mosquitoes in tropical countries causing approximately half a million deaths every year worldwide.
Over six years, the Open Source Malaria (OSM) consortium brought together an international team of researchers who design, synthesise, and test new antimalarial candidates with the hope that they will demonstrate potent activity against Plasmodium falciparum, the deadliest species of the malaria-causing parasite. However, the available experimental bioactivity data is sparse; for all of the different types of experiments that are available, only a very small proportion of the compounds have actually been measured.
Intellegens participated with drug discover partners, Optibrium, in a global challenge organised by the OSM consortium to design new antimalarial compounds with a novel mechanism of action, overcoming the challenge of sparse experimental data. Intellegens and Optibrium achieved joint success in designing a new compound which, when synthesised and tested, has shown good potency. Human chemists familiar with the challenge commented that they would have dismissed the candidate as “ill advised”, demonstrating the potential of Alchemite™ to open up new productive pathways in the drug discovery process.
Publication details
Published in: Journal of Medicinal Chemistry.
Title: An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials
Authors (Intellegens authors in bold): Edwin G. Tse, Laksh Aithani, Mark Anderson, Jonathan Cardoso-Silva, Giovanni Cincilla, Gareth J. Conduit, Mykola Galushka, Davy Guan, Irene Hallyburton, Benedict W. J. Irwin, Kiaran Kirk, Adele M. Lehane, Julia C. R. Lindblom, Raymond Lui, Slade Matthews, James McCulloch, Alice Motion, Ho Leung Ng, Mario Öeren, Murray N. Robertson, Vito Spadavecchio, Vasileios A. Tatsis, Willem P. van Hoorn, Alexander D. Wade, Thomas M. Whitehead, Paul Willis, and Matthew H. Todd
Link: https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.1c00313