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Dual-acting class of antimalarial compounds discovered by Novartis with potential to prevent and treat malaria
Date:11/21/2011

Basel, November 17, 2011 The discovery of a new class of dual-acting antimalarial compounds - the imidazolopiperazines (IZPs) was published in the journal Science online, at the Science Express website today. The findings report on compounds that target both liver and blood infections, attacking the Plasmodium parasite at both stages in its reproduction cycle.

The findings describe how scientists developed a novel assay to determine liver stage activity of candidate small molecules, then used the assay and other tools to identify and optimize a chemical scaffold with activity on both blood- and liver-stage parasites in malaria mouse models. Several other compound classes, also with dual activity, are described and released by Novartis through ChEMBL Neglected Tropical Disease at https://www.ebi.ac.uk/chemblntd.

For over a decade, Novartis has engaged in the front ranks of combating malaria, pioneering the not-for-profit supply of our antimalarial treatment Coartem to the public sector of endemic countries, commented Joseph Jimenez, CEO of Novartis. These new findings further demonstrate our innovative and sustainable research commitment in this important area which has become integral to our corporate strategy for social responsibility.

Scientists from the Novartis Institutes for BioMedical Research, through the Genomics Institute of the Novartis Research Foundation (GNF) and the Novartis Institute for Tropical Diseases (NITD), collaborated with the Scripps Research Institute and Swiss Tropical and Public Health Institute, and received support from the Wellcome Trust, Singapore Economic Development Board, and Medicines for Malaria Venture. This is the second new class of antimalarials discovered by the same group in the last two years and holds promise as a next-generation treatment for malaria if confirmed.

Novartis is committed to the elimination of malaria. Programs with our current anti-malarial treatment have helped save more than one million lives2 to date, but there remains much to be done, said Mark Fishman, NIBR President. Concerns of potential future resistance to current medicines, and the need to treat liver forms of malaria, propel our scientists to devise new medicines. The chemical data from this successful study, and the methods of chemical analysis, have all been released to the public domain. Hopefully, such sharing will facilitate broad-based discovery efforts across the globe towards elimination of this disease.

Researchers believe that future antimalarials will need to work against both blood and liver stages to bring us closer to the goal of eliminating malaria globally. The malaria parasite first infects the liver before moving to red blood cells and causing symptoms. However, after clearance in the blood, reservoirs of parasites can linger in the liver causing relapse and hampering efforts toward complete elimination of the disease. Each year there are about 250 million cases of malaria and nearly one million deaths mostly among children living in Africa3.

It is important to develop new classes of treatment that are one step ahead of the parasite should parasite resistance to current therapies occur, according to researchers In collaboration with research partners, NIBR is working on developing a pipeline of potential new treatment candidates for drug-resistant malaria. Last years development of the spiroindolone class, represented by NITD6094, is now in Phase I human clinical trials, with Phase II expected to commence in early 2012.

Compounds with dual activity are rare among current antimalarials, said Martin Seidel, GNF Institute Director. The activity of the IZP compound class on liver-stage parasites, if it can be confirmed in clinical trials, gives promise to this class as a first-line therapy for the prevention and treatment of malaria.

According to Elizabeth Winzeler, GNF Department Head and lead investigator, Little was known about malaria liver stages when we started this work and as a consequence, we didnt have a good idea about how to approach the problem. Eventually we decided to develop an automated microscopy method to look for compounds that would alter the appearance of the developing liver stages. We are excited that by publishing the full set of compounds active in both blood and liver stages, new targets might be identified.

Broader commitment to fighting malaria: Novartis Malaria Initiative

This research is part of a broader commitment by Novartis in the fight against malaria. The Novartis Malaria Initiative is one of the pharmaceutical industrys largest access-to-medicines programs, focused on treatment, access, capacity-building and research & development. Over the last decade, the initiative has delivered over 400 million treatments without profit to the public sector, in more than 60 countries, has helped save more than one million lives2. Novartis believes that increasing access to medicines in developing countries is not just a matter of buying medicines and distributing them, it also requires bringing together good clinical practice, logistics management and other expertise to ensure a long-term sustainable approach to improving health. For more information visit www.malaria.novartis.com.


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Contact: Mariellen Gallagher
mariellen.gallagher@novartis.com
617-871-7665
Novartis Institutes for BioMedical Research
Source:Eurekalert

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