KAF-156




IUPAC name: 2-Amino-1-(2-(4-fluorophenyl)-3-((4-fluorophenyl)amino)-5,6-dihydro-8,8-dimethylimidazo(1,2-a)pyrazin-7(8H)-yl)ethanone 

Molecular formula: C22H23F2N5O


Molecular weight: 411.4 g/mol


Synonyms: Ganaplacide, KAF-156, GNF-156, GNF 156



SMILES: CC1(C2=NC(=C(N2CCN1C(=O)CN)NC3=CC=C(C=C3)F)C4=CC=C(C=C4)F)C


Developmental Status: Phase IIb combination study ongoing


Company: Discovery partnership between MMV, Wellcome Trust, Novartis, and the Swiss Tropical and Public Health Institute


Description: The imidazolopiperazine compound KAF156 belongs to a new class of antimalarial agents with activity against asexual and sexual blood stages and the pre-erythrocytic liver stages of malarial parasites. According to studies, KAF156 displayed activity against vivax and falciparum malaria, including artemisinin-resistant parasites. (White, N.J. et al., 2016).

Mechanism of action: The mechanism of action of KAF156 could not yet be determined. Decreased susceptibility to KAF156 is associated with mutations in three P. falciparum genes, CARL (cyclic amine resistance locus), UDP-galactose and Acetyl-CoA transporters.

Activity: KAF156 displays blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains (Kuhen, K. L. et al., 2014).

KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo.

KAF156 displays cidal activity against mature Plasmodium falciparum gametocytes and thus blocks parasite transmission to Anopheles mosquitoes.

References:

Kuhen, K. L. et al. (2014) KAF156 is an Antimalarial Clinical Candidate with Potential for Use in Prophylaxis, Treatment, and Prevention of Disease Transmission. Antimicrobial Agents and Chemotherapy. 58(9),  5060-5067. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135840/pdf/zac5060.pdf)

White, N.J. et al. (2016) Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. N Engl J Med. 375(12), 1152-1160. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142602/pdf/emss-70306.pdf)

Medicines for Malaria Venture. (https://www.mmv.org/related-story-type/kaf156)


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