pyrimethamine   

GtoPdb Ligand ID: 4800

Synonyms: Daraprim® | GNF-Pf-5586 | TCMDC-125860
pyrimethamine is an approved drug (FDA (1953))
Compound class: Synthetic organic
Comment: Pyrimethamine is an antifolate compound with broad-spectrum antiprotozoal activity. It is used in the treatment and prevention of malaria as part of a combination therapy.

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: pyrimethamine

2D Structure
Click here for structure editor
Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 2
Topological polar surface area 77.82
Molecular weight 248.08
XLogP 2.68
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CCc1nc(N)nc(c1c1ccc(cc1)Cl)N
Isomeric SMILES CCc1nc(N)nc(c1c1ccc(cc1)Cl)N
InChI InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
InChI Key WKSAUQYGYAYLPV-UHFFFAOYSA-N
Bioactivity Comments
The whole organism assay data in the interactions table below, provides an evaluation of the antimalarial (asexual blood stage) activity of pyrimethamine using a panel of culture-adapted P. falciparum strains. Pyrimethamine demonstrates reduced potency against drug resistant strains.
Selectivity at transporters
Key to terms and symbols Click on species/strain names for details Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Multidrug and toxin extrusion Hs Inhibitor Inhibition 7.1 pKi - 2
pKi 7.1 (Ki 7.7x10-8 M) [2]
MATE2 Mm Inhibitor Inhibition 6.3 pKi - 2
pKi 6.3 (Ki 4.6x10-7 M) [2]
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
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfD6 Parasite growth inhibition assay - - 8.3 pIC50 - 1
pIC50 8.3 (IC50 4.6x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfNF54 Parasite growth inhibition assay - - 7.8 pIC50 - 1
pIC50 7.8 (IC50 1.7x10-8 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfTM4 Parasite growth inhibition assay - - 7.2 pIC50 - 5
pIC50 7.2 (IC50 5.8x10-8 M) [3H]-hypoxanthine incorporation assay using wild-type P. falciparum (TM4) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Pf7G8 Parasite growth inhibition assay - - 5.2 pIC50 - 1
pIC50 5.2 (IC50 6.689x10-6 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfTM90C2A Parasite growth inhibition assay - - 5.1 pIC50 - 1
pIC50 5.1 (IC50 8.231x10-6 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfK1 Parasite growth inhibition assay - - <5.0 pIC50 - 1
pIC50 <5.0 (IC50 >1x10-5 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfW2 Parasite growth inhibition assay - - <5.0 pIC50 - 1
pIC50 <5.0 (IC50 >1x10-5 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase PfV1/S Parasite growth inhibition assay - - <4.0 – 5.0 pIC50 - 1,5
pIC50 <5.0 (IC50 >1x10-5 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
pIC50 <4.0 (IC50 >1x10-4 M) [3H]-hypoxanthine incorporation assay using quadruple mutant P. falciparum (V1/S) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)