Principal Investigator (PI)
The Foundation is providing £379,633 in support.
Abbas Hussein Khamis Al Temimi
Pedro Martin
MedChem and ADME/preliminary safety mentoring and advising.
Providing assay ready library plates for screening against validated targets (primary screening and analogues for validation and SAR expansion)
Support for the development and miniaturization of quantitative assays for screening against targets that are still undergoing further validation
The escalating incidence of resistance to the front-line drugs highlights the urgent need to identify new chemotherapeutic options, preferably with modes of action (MoA) that differ from those of the currently used antimalarial drugs. Exploring novel targets presents one attractive strategy towards drug development. The discovery of critical targets for Plasmodium survival and disease transmission allows us to design new targetbased screenings with guarantees to identify novel quality chemical classes with potential to avoid infection, kill the parasite and/or avoid transmission. This proposal aims to leverage on existing knowledge about Plasmodium essential targets to refill the antimalarial pipeline with novel chemical diversity with the desired profile.
By engaging in a unique transnational co-fund collaborative arrangement, Tres Cantos Open Lab Foundation and the Malaria Drug Accelerator (MALDA) consortium funded by the Bill and Melinda Gates Foundation will undertake a milestone-based program designed to maximize outputs and impact. The project aims to couple screening activities on the ‘top’ targets identified by the consortium and medicinal chemistry efforts that allow to validate phenotypically the hits resulting from the screening as well as advance chemical matter already identified.
ABOUT MALDA
The Malaria Drug Accelerator is a consortium of 14 laboratories, led by Dr. Elizabeth Winzeler at the University of California, San Diego, whose mission is the identification of new starting points for antimalarial drugs that can be used in eradication and elimination. Much of the focus is on finding “chemicallyvalidated” high value drug targets that can be used in structure-guided drug discovery. The consortium begins with compounds, often identified in phenotypic screens, or through academic collaborations that may be chemically intractable, but which have pan-activity across the malaria lifecycle. The consortium then identifies the “target” using either in vitro selections or proteomic. Next, the consortium seeks to develop a biochemical assay that can be used to monitor direct inhibition of the target. Once an assay is ready, screens can be runand potential hit compounds identified. Subsequent Hit-to-Lead and delivery of early leads to global malaria pipeline are also key aspects of MalDA mission.
A collaboration between TCOLF and MalDA offers many advantages to both parties. Having attractive and diverse chemical libraries as well as medicinal chemists who can help with hit selection and initial optimization is a first step toward moving compounds toward development and thus meeting MalDA and BMGF overarching goals. MalDA, on the other hand, retains state-of-the-art expertise in malaria parasite biology and provides a superb environment as well as training and support for MalDA-associated fellows. MalDA members have expertise with all types of parasite genetic engineering, protein expression, and chemo- and bio-informatics.