Australian researchers for tropical disease

This medical condition is currently endemic in 21 countries across Latin America killing more people in the region each year than any other parasite-born disease including malaria. Moreover its prevalence is growing in non-endemic developed countries including Australia, USA, Japan, Spain and more with around 8 million cases and 100 million people at risk.

The novel compounds identified demonstrated oral activity in an in-vivo mouse model of T. cruzi infection, suppressing bloodstream parasitemia to virtually undetectable levels after once-a-day dosing for 10-days. Compounds are potent (nM IC50 ‘s), selective for T. cruzi parasites, are non-cytoxic EBIs with improved CYP3A4 profiles and are straight forward to synthesize allowing rapid optimization of target biological activity and drug characteristics.

Research began July 2008 when Epichem was contracted in the amount of AUD$2.7 million by the Swiss based not-for-profit organization – Drugs for Neglected Diseases initiative (DNDi) to identify a new cost effective medicine to treat the chronic phase of Chagas. The only available medicines for treatment are benznidazole and nifurtimox, which treat the acute phase and have poor patient compliance due to various side effects.

Drug discovery efforts have been collaborative with DNDi, a team of parasitologists from Murdoch University (Western Australia), pharmaceutical scientists at the Centre for Drug Candidate Optimisation (Monash University, Melbourne Australia) and recently with another group in Brazil (Universidade Federal de Ouro Preto).

According to Epichem’s Head of Drug Discovery, Dr Martine Keenan, “The collaboration has worked exceptionally well due to the high levels of professional interaction, enthusiasm, availability and timeliness of testing and the goal oriented atmosphere. Importantly, the flexibility of working in a small and highly dedicated team of only 5 chemists in an intellectually unconstrained environment contributed to our success, as we were able to follow exactly where the data took us. We started with nothing in 2008 and in 3 months we had identified an exciting hit molecule fenarimol, a sterol biosynthesis inhibitor. Within 18 months the project had exemplified 4 related chemical scaffolds and quickly moved forward to produce biological activity in the mouse model.”


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