Optimisation of phosphodiesterase inhibitors to provide in vivo proof of concept for development of a new antimalarial drug

The World Health Organization estimated that there were around 200 million cases of malaria resulting in over 400,000 deaths in 2015. Drug resistant malaria parasites are widespread and so new antimalarial drugs are needed urgently. David Baker from the London School of Hygiene & Tropical Medicine (LSHTM) is leading a team that will use an Innovator Award to develop a class of potential drugs that block the activity of malaria parasite enzymes known as phosphodiesterases (PDEs). The team have identified a series of small molecule inhibitors which target the malaria parasite PDEs. Some of these compounds potently block development of blood stage parasites (that cause disease symptoms) and of sexual stage parasites (that mediate transmission to mosquitoes). One of the major advantages of this strategy is that safe drugs that target PDEs are already in use in the clinic to treat other human diseases and disorders. As part of the Innovator Award, chemists at the not for profit company Salvensis will design numerous novel versions of these promising compounds to be tested for activity on malaria parasites at the LSHTM and at other institutions around the world in assays funded by the Medicines for Malaria Venture (MMV). The longer-term hope is to develop a new dual-action antimalarial drug that can both treat individual patients and break the cycle of transmission in the wider population.

Project details

Drug-based Strategies
Product Development

Jan 2019 — Sep 2021

$657,677

United Kingdom