Monash University

Start : March 2015 | Status : Complete

The scientist: Dr. Kevin Neildé will focus his research on the discovery of new drugs for Chagas disease, through a project titled "Hit to Lead Optimization for kinetoplastid diseases: single agents for Chagas”. Kevin is Postdoctoral Researcher at the Monash Institute of Pharmaceutical Science (Monash University, Australia) with Prof. Jonathan Baell, and has extensive experience in organic synthesis and design of biologically active compounds.

The sponsors: The Monash Institute of Pharmaceutical Science focus on medicinal chemistry for drug discovery. Research is both fundamentally focused – on chemistry and structure-based drug design – and translational. Working in a multidisciplinary, iterative feedback cycle of design, synthesis and biological testing, the objective is to optimise the potency, selectivity and bioavailability of a compound, while minimising side-effects. Monash´ research programs are undertaken with key industry partners, including biotechnology companies, large pharmaceutical companies and leading research institutions.

Foundation funding: The Foundation is providing £103,070 in support.

GSK’s contribution: GSK is providing in-kind contributions, including scientific expertise in T.cruzi in vitro assays, medicinal chemistry, DMPK and further profiling activities. GSK will provide access to the relevant facilities as well as the necessary laboratory supplies to carry out the different work packages.

Project Description: Trypanosoma cruzi is the causative agent of Chagas disease, which is spread by the bite of the assassin beetle (“kissing bug”) and endemic in 18 countries in Latin America. It is responsible for approximately 14,000 deaths and a disease burden of 0.7 million DALYs annually. It is also a primary cause of cardiomyopathy in the Americas.
Two therapies are currently used for Chagas disease: nifurtimox and benznidazole. These drugs have adverse side-effects and they neither prevent the development of, nor can treat, chronic Chagas disease. There is a critical need for new treatment options for this neglected disease.

Researchers at Monash University, led by Pr. J.Baell, and University of Western Australia, led by Dr. Matthew Piggott, have recently identified compounds that show in vitro selective efficacy against T. cruzi and that have appropriate physico-chemical properties to be further progressed. In the frame of this project, two chemical series will be fully profiled and SAR studies established to optimize the hit compounds reach a good in vivo activity and fulfill the criteria for further development into lead compounds.