Cipargamin (NITD609, KAE609) is an experimental synthetic

antimalarial Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young ...

drug belonging to the

spiroindolone The spiroindolones are a class of compounds in which an indolone ring is substituted with another ring in a spiro arrangement. Alkaloids in this class include horsfiline, rhynchophylline, gelsemine, carapanaubine, and maremycin E. Spiroindol ...

class.{{cite journal, title=Spiroindolones, a potent compound class for the treatment of malaria , journal=Science , year=2010 , volume=329 , issue=5996 , pages=1175–80 , pmid=20813948 , doi=10.1126/science.1193225, vauthors=Rottmann M, McNamara C, Yeung BK, Lee MC, Zou B, Russell B, Seitz P, Plouffe DM, Dharia NV, Tan J, Cohen SB, Spencer KR, González-Páez GE, Lakshminarayana SB, Goh A, Suwanarusk R, Jegla T, Schmitt EK, Beck HP, Brun R, Nosten F, Renia L, Dartois V, Keller TH, Fidock DA, Winzeler EA, Diagana TT, author25-link=David A. Fidock , pmc=3050001, bibcode=2010Sci...329.1175R The compound 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 The Biomedical Primate Research Centre (BPRC) is Europe's largest primate animal testing research centre. It is a scientific research institute that performs research that contributes to the identification and development of new medicines against ...

and the Swiss Tropical Institute. Cipargamin is a 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 '' Plasmodium falciparum'' growth in a high throughput

phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

screen of natural products conducted at the Genomics Institute of the Novartis Research Foundation in San Diego, California in 2006. Cipargamin was discovered by screening the Novartis library of 12,000 natural products and synthetic compounds to find compounds active against '' Plasmodium falciparum''. The first screen turned up 275 compounds and the list was narrowed to 17 potential candidates. The current

was optimized to address its metabolic liabilities leading to improved stability and exposure levels in animals. As a result, cipargamin is one of only a handful of molecules capable of completely curing mice infected with ''

Plasmodium berghei ''Plasmodium berghei'' is a species in the genus ''Plasmodium'' subgenus '' Vinckeia''. It is a protozoan parasite that causes malaria in certain rodents. Originally, isolated from thicket rats in Central Africa, ''P. berghei'' is one of four ' ...

'' (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, cipargamin would be the first antimalarial not belonging to either the

artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to '' Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her ...

or peroxide class to go into a proof-of-concept study in malaria. If cipargamin 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. Cipargamin also has properties which could enable it to be manufactured in pill form and in large quantities. Further animal studies have been performed and researchers have begun human-stage trials.

References

Antimalarial agents Tryptamines Chloroarenes Spiro compounds Novartis brands Fluoroarenes