Cipargamin

NITD609 is a synthetic antimalarial molecule belonging to the spiroindolone class.

The compound, dubbed NITD609, was developed at the Novartis Institute for Tropical Diseases in Singapore, through a collaboration with the Genomics Institute of the Novartis Research Foundation (GNF), the Biomedical Primate Research Centre (BPRC) and the Swiss Tropical Institute (STI).

The drug was discovered by screening the Novartis library of 12,000 natural products and synthetic compounds to find compounds active against the most deadly malaria parasite.

The first screen turned up 275 compounds and the list was narrowed to 17 potential candidates.

"From the beginning, NITD609 stood out because it looked different, in terms of its structure and chemistry, from all other currently used antimalarials," Elizabeth Winzeler said in a statement.

"The ideal new malaria drug would not just be a modification of existing drugs, but would have entirely novel features and mechanism of action. NITD609 does."

Further animal studies are underway and researchers are in the process of getting approval for early-stage human trials.

NITD609 is a novel, synthetic antimalarial molecule belonging to the spiroindolone class, awarded MMV Project of the Year 2009. It is structurally related to GNF 493, a compound first identified as a potent inhibitor of P. falciparum growth in a high throughput phenotypic screen of natural products conducted at the Genomics Institute of the Novartis Research Foundation (GNF) in San Diego, California in 2006.

The current spiroindolone was optimized to address its metabolic liabilities leading to improved stability and exposure levels in animals. As a result, NITD609 is one of only a handful of molecules capable of completely curing mice infected with Plasmodium berghei – a model of blood-stage malaria. Given its good physicochemical properties, promising pharmacokinetic and efficacy profile, the molecule was recently approved as a preclinical candidate and is now entering GLP toxicology studies with the aim of entering Phase I studies in humans in late 2010. If its safety and tolerability are acceptable, NITD609 would be the first antimalarial not belonging to either the artemisinin or peroxide class to go into a proof-of-concept study in malaria.

The experimental drug NITD609 belongs to a new class of drugs called spiroindolenes. It was identified by the Novartis Institute for Tropical Diseases (NITD) working in an international collaboration supported by the Wellcome Trust, the international Medicines for Malaria Venture (MMV), the U.S. National Institutes of Health (NIH) and several other bodies.

Anthony Fauci, director of the NIH's National Institute of Allergy and Infectious Diseases, said the experimental compound had several "desirable features," including that it targets a parasite protein not attacked by any existing malaria drugs.

NITD609 also has properties which could enable it to be manufactured in pill form and in large quantities.

If NITD609 behaves similarly in people to the way it works in mice, it may be possible to develop it into a drug that could be taken just once - far easier than current standard treatments in which malaria drugs are taken between one and four times a day for up to seven days.

See also

• Malaria
• Spiroindolone