ACT-451840

Ligand id: 10022

Name: ACT-451840

Structure and Physico-chemical Properties

2D Structure
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

View interactive charts of activity data from GtoPdb and ChEMBL (where available) across species

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
Key to terms and symbols Click on species/strain names for details Click column headers to sort
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)