ACT-451840

Ligand id: 10022

Name: ACT-451840

Structure and Physico-chemical Properties

2D Structure
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Calculated Physico-chemical Properties
Hydrogen bond acceptors 9
Hydrogen bond donors 0
Rotatable bonds 15
Topological polar surface area 91.2
Molecular weight 750.43
XLogP 7.49
No. Lipinski's rules broken 2

Molecular properties generated using the CDK

Bioactivity Comments
The interaction table below provides data from whole cell assays and gives the antiparasite activitity of ACT-451840 against a number of Plasmodium lifecycle stages. The results include an evaluation of asexual blood stage activity using a panel of culture-adapted P. falciparum strains, with ACT-451840 demonstrating no evidence of reduced potency against drug resistant strains. Results from assays measuring the effect of ACT-451840 on the functional viability of mature gametocytes and oocysts of P. falciparum indicate that the transmission-blocking effect is dependent on the gametocytocidal activity of the compound.
Whole organism assay data
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MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA PfW2 Parasite growth inhibition assay - - 9.7 pIC50 - 7
pIC50 9.7 (IC50 2x10-10 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfV1/S Parasite growth inhibition assay - - 9.5 pIC50 - 7
pIC50 9.5 (IC50 3x10-10 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfK1 Parasite growth inhibition assay - - 9.5 pIC50 - 7
pIC50 9.5 (IC50 3x10-10 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA Pf7G8 Parasite growth inhibition assay - - 9.5 pIC50 - 7
pIC50 9.5 (IC50 3x10-10 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfNF54 Parasite growth inhibition assay - - 9.4 pIC50 - 7
pIC50 9.4 (IC50 4x10-10 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfD6 Parasite growth inhibition assay - - 9.3 pIC50 - 7
pIC50 9.3 (IC50 5x10-10 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfTM90C2A Parasite growth inhibition assay - - 9.0 pIC50 - 7
pIC50 9.0 (IC50 1x10-9 M) [3H]-hypoxanthine incorporation [7]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfNF54 Parasite dual gamete formation assay (DGFA) - - 8.2 pIC50 - 7
pIC50 8.2 (IC50 5.89x10-9 M) male gamete formation from the gametocyte stage [7]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Conditions: ACT-451840 had no effect on the functional viability of female gametocytes up to a concentration of 20 μM.
Unknown MOA Pf Standard membrane feeding assay (SMFA) - - 7.5 pIC50 - 7
pIC50 7.5 (IC50 3x10-8 M) Indirect mode: dose-dependent inhibition of oocyst development in the mosquito was observed. Direct mode: no activity at concentrations up to 1 μM [7]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)