Chemistry for Life/Chemistry for Medicine Seminar

Despite substantial scientific progress over the past decade, new, affordable and safe malaria medicines are urgently required to overcome increasing resistance against artemisinin based combination treatments, treat vulnerable populations, interrupt the parasite life cycle by blocking transmission to the vectors, prevent infection and target malaria species that transiently remain dormant in the liver.¹

Advances in our understanding of the underlying molecular basis of malaria has accelerated the development of new drugs. Several new combination therapies are in clinical development that have efficacy against drug-resistant parasites and the potential to be used in single-dose regimens to improve compliance. A step change in assay technology and reduction in screening costs to $1 per data point, coupled with collaborative drug discovery projects has enabled the testing of large compound collections. To date, in excess of 9 million compounds have been screened against the P. falciparum blood stage of malaria and more than 25,000 hits identified with IC₅₀ values < 1 µM. Drug discovery projects starting from the hit series has led to the identification of > 15 drug candidates that have been progressed to clinical development. The most advanced of these candidates are now in Phase II clinical trials.² In addition, chemogenomic methods have enabled the discovery of > 15 new drug targets and mechanism of action from the same pool of compounds. Lessons can be learnt from these projects, and it is hoped that this knowledge can be used to increase the likelihood of continued discovery of safe, effective, and affordable antimalarial medicines in the future.

1. Phillips, M. A., Burrows, J. N., Manyando, C., van Huijsduijnen, R. H., Van Voorhis, W. C., & Wells, T. N. C. (2017). Malaria. Nature Reviews Disease Primers, 3, 17050.

https://www.mmv.org/research-development/mmv-supported-projects