Dundee: The details of the discovery, properties and mechanism of action of a novel antimalarial compound, DDD107498, have been published in the journal Nature. DDD107498 has the potential to treat malaria patients in a single dose, including those with malaria parasites resistant to current medications, and help reduce the transmission of the parasite. The compound was identified through a collaboration between the University of Dundee’s Drug Discovery Unit (DDU) and Medicines for Malaria Venture (MMV).
“The publication describes the discovery and profiling of this
exciting new compound,” said Professor Ian Gilbert, Head of Chemistry at
the Drug Discovery Unit, who led the team that discovered the compound.
“It reveals that DDD107498 has the potential to treat malaria with a
single dose, prevent the spread of malaria from infected people, and
protect a person from developing the disease in the first place.
“There is still some way to go before the compound can be given to
patients. However we are very excited by the progress that we have
“Malaria continues to threaten almost half of the world’s population –
the half that can least afford it,” said Dr David Reddy, MMV’s CEO.
“DDD107498 is an exciting compound since it holds the promise to not
only treat but also protect these vulnerable populations. The
collaboration to identify and progress the compound, led by the Drug
Discovery Unit at the University of Dundee, drew on MMV’s network of
scientists from Melbourne to San Diego. The publication of the research
is an important step and a clear testament to the power of
Dr Kevin Read, joint leader of the project, also based at the Drug
Discovery Unit at Dundee, said, “New drugs are urgently needed to treat
malaria, as resistance to the current gold-standard antimalarial drug is
now considered a real threat. The compound we have discovered works in a
different way to all other antimalarial medicines on the market or in
clinical development, which means that it has great potential to work
against current drug-resistant parasites. It targets part of the
machinery that makes proteins within the parasite that causes malaria.”
“The need for new antimalarial drugs is more urgent than ever before,
with emerging strains of the parasite now showing resistance against
the best available drugs,” said Dr Michael Chew from the Wellcome Trust,
which provides funding for the Dundee DDU and MMV. “These strains are
already present at the Myanmar-Indian border and it’s a race against
time to stop resistance spreading to the most vulnerable populations in
Africa. The discovery of this new antimalarial agent, which has shown
remarkable potency against multiple stages of the malaria lifecycle, is
an exciting prospect in the hunt for viable new treatments.”
“Our partnership with MMV was critical to the progress of this
compound,” added Professor Ian Gilbert. “Dr Paul Willis at MMV and Sir
Simon Campbell, a mentor from MMV’s Expert Scientific Advisory
Committee, gave invaluable input to the project. We have extensively
profiled the compound, investigating its properties to understand how it
works; this could not have been done without MMV’s scientific input and
support of its network of partners around the world.”
ABOUT THE TOPIC
The World Health Organisation reports 200 million clinical cases of
malaria in 2013, with 584,000 people dying from the disease. Most of
these deaths were children under the age of 5 and pregnant women.
The University of Dundee team has been working with MMV since 2009 to
identify potential new treatments for malaria. The project was
initiated by testing a collection of around 4,700 compounds at the
University of Dundee Drug Discovery Unit to see if any would kill the
malaria parasite. From this screening, the chemical starting point was
identified and then optimised through cycles of design, preparation and
testing, by a team of chemists and biologists.
In October 2013, MMV selected DDD498 to enter preclinical development
following the recommendation of its Expert Scientific Advisory
Committee. Since then, with MMV’s leadership, large quantities of the
compound have been produced and it is undergoing further safety testing
with a view to entering human clinical trials within the next year.
In a critical next step
in the progression of DDD107498, Merck Serono has recently obtained the
right to develop and, if successful, commercialize the compound, with
the input of MMV’s expertise in the field of malaria drug development
and access and delivery in malaria-endemic countries.