Parasitic infections cause a tremendous burden of disease in both the tropics and subtropics as well as in more temperate climates. Of all parasitic diseases, malaria causes the most deaths globally. Malaria kills approximately 660,000 people each year, most of them young children in sub-Saharan Africa.
The Neglected Tropical Diseases (NTDs), which have suffered from a lack of attention by the public health community, include parasitic diseases such as lymphatic filariasis, onchocerciasis, and Guinea worm disease. The NTDs affect more than 1 billion people—one-sixth of the world’s population—largely in rural areas of low-income countries. These diseases extract a large toll on endemic populations, including lost ability to attend school or work, retardation of growth in children, impairment of cognitive skills and development in young children, and the serious economic burden placed on entire countries.
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An antitrypansomal drug that also possesses antitumor activity; inhibits CRL (Cullin-RING E3 ubiquitin ligases) activity by disrupting its ability to recruit Cdc34; induces accumulation of CRL substrates; also inhibits multiple viruses (ZIKVs, EV71).
Suramin sodium salt
Suramin sodium salt (BAY-205, NF-060) is an antitrypansomal drug that also possesses antitumor activity; inhibits CRL (Cullin-RING E3 ubiquitin ligases) activity by disrupting its ability to recruit Cdc34; induces accumulation of CRL substrates; also inhibits multiple viruses (ZIKVs, EV71).
Tizoxanide is the main metabolite of nitazoxanide, which is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent.
Artefenomel (OZ439) is a novel, next-generation antimalarial ozonide that demonstrates high potentcy against P. falciparum in vitro and P. berghei in vivo (K1/NF54, IC50=2.0/3.2 nM).
Cipargamin (KAE609, NITD609) is a fast-acting, potent antimalarial agent that inhibits blood-stage activity in vitro against a panel of culture-adapted P. falciparum strains with IC50 of 0.5-1.4 nM; inhibits the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM; also is a very effective drug in reducing transmission to the Anopheles stephensi mosquito vector; shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in rodent malaria model.
Ganaplacide (KAF156, GNF-156) is a novel antimalarial clinical candidate that shows blood schizonticidal activity with IC50 of 6-17.4 nM against P falciparum drug-sensitive and drug-resistant strains; demonstrates potent therapeutic activity in mouse models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively; KAF156 is completely protective as a single oral dose of 10 mg/kg in sporozoite challenge mouse model; shows the potential to treat, prevent, and block the transmission of malaria.
Emodepside is a semisynthetic derivative of PF1022A, and novel cyclo-depsipeptide anthelmintic which is efficacious against a variety of gastrointestinal nematodes; causes parasitic nematode muscle relaxation, inhibition of muscle contraction elicited by either ACh or the neuropeptide AF2; elicits a Ca(++)-dependent hyperpolarization of muscle cells.
DSM265(DSM-265;DSM 265) is a potent, highly selective, long-duration and orally bioavailable malaria DHODH (PfDHODH) inhibitor with IC50 of 0.01 ug/mL; displays excellent selectivity versus human DHODH; potently kills both sensitive and drug resistant strains of the parasite with EC50 of 0.001-0.004 ug/ml; has favorable pharmacokinetic properties and efficacious against both blood and liver stages of P. falciparum in vivo.
MMV390048(MMV 048;MMV 390048) is a novel potent Plasmodium PI4K inhibitor with IC50 of 28 nM against intraerythrocytic life cycle stages of P. falciparum (NF54 drug-sensitive strain); blocks all life cycle stages of the malaria parasite, exhibits full chemoprotection, delays relapse in a Plasmodium cynomolgi monkey model.
Tafenoquine (SB-252263, Tafenoquine, WR 238605) is a long-acting, orally active anti-malarial agent to prevent malaria that is holoendemic for Plasmodium falciparum.
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