KDU691   Click here for help

GtoPdb Ligand ID: 11863

Antimalarial Ligand
Compound class: Synthetic organic
Comment: KDU691 is an inhibitor of P. falciparum phosphatidylinositol 4-kinase beta (PfPI4Kβ) with a novel imidazopyrazine core [2].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 79.6
Molecular weight 419.11
XLogP 3.62
No. Lipinski's rules broken 0
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Canonical SMILES CNC(=O)c1ccc(cc1)c1cnc2n1cc(nc2)C(=O)N(c1ccc(cc1)Cl)C
Isomeric SMILES CNC(=O)c1ccc(cc1)c1cnc2n1cc(nc2)C(=O)N(C)c1ccc(cc1)Cl
InChI InChI=1S/C22H18ClN5O2/c1-24-21(29)15-5-3-14(4-6-15)19-11-26-20-12-25-18(13-28(19)20)22(30)27(2)17-9-7-16(23)8-10-17/h3-13H,1-2H3,(H,24,29)
Bioactivity Comments
The interaction table below provides data from whole cell assays and gives the antiparasite activity of KDU691 against a number of Plasmodium lifecycle stages. In addition, KDU691 is reported to have potent activity against both P. malariae (median ex vivo IC50 of 10.04 nM) and P. falciparum (median ex vivo IC50 of 7.38 nM) Malian field isolates [1].
Whole organism assay data
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MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Plasmodium falciparum phosphatidylinositol 4-kinase beta Pf Parasite growth inhibition assay - - 7.5 pIC50 - 2
pIC50 7.5 (IC50 2.99x10-8 M) SYBR Green assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum phosphatidylinositol 4-kinase beta Py Parasite liver stage assay - - 7.4 pIC50 - 2
pIC50 7.4 (IC50 3.6x10-8 M) Sporozoite hepatocyte invasion assay [2]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
Plasmodium falciparum phosphatidylinositol 4-kinase beta Pc Parasite liver stage assay - - ~6.7 pIC50 - 2
pIC50 ~6.7 (IC50 ~1.96x10-7 M) P. cynomolgi infected primary rhesus hepatocyte assay to assess activity against hypnozoites [2]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
Plasmodium falciparum phosphatidylinositol 4-kinase beta PfNF54 Parasite late stage (III–V) gametocyte assay - - 6.7 pIC50 - 2
pIC50 6.7 (IC50 2.2x10-7 M) Parasite lactate dehydrogenase (pLDH) assay [2]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)