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J Parasit Dis Diagn Ther 2017
Volume 2 Issue 3
September 7-8, 2017 | Edinburgh, Scotland
4th International Conference on
Tropical Medicine, Infectious Diseases & Public Health
Notes:
Tropical Medicine 2017
Sergio Wittlin, J Parasit Dis Diagn Ther 2017
NOVEL ANTIMALARIAL COMPOUND ACT-451840:
PRECLINICAL ASSESSMENT
Addressing the urgent need for the development of new
antimalarials, a chemical class of potent antimalarial
compounds with a novel mode of action was recently
identified. Here, the preclinical characterization of one of
these compounds, ACT-451840, conducted in partnership
with academic and industrial groups is presented. The
properties of ACT-451840 are described, including its
spectrum of activities against multiple life cycle stages of the
human malaria parasite Plasmodium falciparum (asexual
and sexual) and Plasmodium vivax (asexual) as well as
oral in vivo efficacies in two murine malaria models that
permit infection with the human and the rodent parasites P.
falciparum and Plasmodium berghei, respectively. In vitro,
ACT-451840 showed a 50% inhibition concentration of 0.4
nM against the drug-sensitive P. falciparum NF54 strain. The
90% effective doses in the in vivo efficacy models were 3.7
mg/kg against P. falciparum and 13 mg/kg against P. berghei.
ACT-451840 potently prevented male gamete formation from
the gametocyte stage with a 50% inhibition concentration of
6 nM and dose-dependently blocked oocyst development
in the mosquito with a 50% inhibitory concentration of 30
nM. The compound's preclinical safety profile is presented
and is in line with the published results of the first-in-man
study in healthy male participants, in whom ACT-451840
was well tolerated. The fast parasite reduction ratio (PRR)
and gametocytocidal effect of ACT-451840 were recently also
confirmed in a clinical proof-of-concept (POC) study.
Biography
Sergio Wittlin is a group leader at the Swiss Tropical and Public Health Institute (Swiss
TPH). He received his PhD in biochemistry from the Biozentrum of the University of
Basel, Switzerland in 1999 and obtained a 3 years of postdoctoral experience in molec-
ular genetics at the Walter and Eliza Hall Institute at Melbourne, Australia. In 2002 he
moved to the Swiss TPH, where his research is focused on the malaria parasite in cell
culture assays and mouse models, with the ultimate aim to discover new antimalarial
drugs in a multidisciplinary approach. In 15 years of collaboration with the Medicines for
Malaria Venture (MMV) in Geneva, his laboratory was significantly involved in moving 4
compounds in the MMV pipeline into clinical trials.
Sergio Wittlin
Swiss Tropical and Public Health Institute, Switzerland