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Compound Detail

CHEMBL36

PYRIMETHAMINE
💊 Approved Drug
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💊 Approved Drug
CCc1nc(N)nc(N)c1-c1ccc(Cl)cc1

Basic Information

ChEMBL ID CHEMBL36
Name PYRIMETHAMINE
Phase Approved
Structure Type MOL
InChI Key WKSAUQYGYAYLPV-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Chloridine Daraprim GNF-PF-5586 Malacide NSC-3061 Pirimetamina Pyrimethamine Pyrimethamine component of fansidar Pyrimethaminum RP-4753 TCMDC-123831 TCMDC-125860 +1 more
227
Targets
734
Activities
4
Assay Types
5
PK Parameters
20
Publications
13
Known Names
20
Indications
1
Mechanisms

Molecular Properties

248.7
MW (Da)
2.52
ALogP
4
HBA
2
HBD
77.8
PSA (Ų)
0.86
QED
0
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1953
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Natural Product

Extended Properties

Molecular Formula C12H13ClN4
MW 248.72
Aromatic Rings 2
Heavy Atoms 17
NP-Likeness -0.93

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dihydrofolate reductase inhibitor INHIBITOR Bifunctional dihydrofolate reductase-thymidylate synthase

Indications

Malaria Toxoplasmosis Anemia Chorioretinitis Depressive Disorder HIV Infections HIV Infections Malaria, Falciparum Malaria, Vivax Pneumonia, Pneumocystis Pregnancy Premature Birth Schistosomiasis Schizophrenia Toxoplasmosis, Congenital Toxoplasmosis, Cerebral Amyotrophic Lateral Sclerosis Gangliosidoses, GM2 Leukemia, Lymphocytic, Chronic, B-Cell Myelodysplastic Syndromes

ATC Classification

P01BD01
pyrimethamine
Level 1: ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
Level 2: ANTIPROTOZOALS
P01BD51
pyrimethamine, combinations
Level 1: ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
Level 2: ANTIPROTOZOALS

Activity Summary

IC50 640 meas. best 10.55
Ki 55 meas. best 9.72
EC50 35 meas. best 7.84
Kd 4 meas. best 8.85

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Plasmodium falciparum
CHEMBL364
IC50 10.55 6.9516 0.0 121
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1939
Ki 9.72 8.0028 0.2 18
Unchecked
CHEMBL612545
Ki 9.23 7.7778 0.6 18
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL4296323
Ki 9.07 9.07 0.8 1
Dihydrofolate reductase
CHEMBL1809
Ki 8.92 7.89 1.2 5
Dihydrofolate reductase
CHEMBL1809
Kd 8.85 8.34 1.4 4
Unchecked
CHEMBL612545
IC50 8.8 6.4382 1.6 28
Plasmodium yoelii
CHEMBL612889
IC50 8.67 8.67 2.2 1
HEK293
CHEMBL614818
IC50 8.38 6.375 4.2 6
Plasmodium berghei
CHEMBL612653
IC50 8.33 8.33 4.7 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1939
IC50 8.28 6.2913 5.2 8
Dihydrofolate reductase
CHEMBL202
Ki 8.1 7.2811 8.0 9
Enterococcus faecium
CHEMBL357
IC50 8.1 6.54 8.0 2
Dihydrofolate reductase
CHEMBL1926
Ki 8.01 8.01 9.7 1
Plasmodium falciparum
CHEMBL364
EC50 7.84 7.2656 14.6 9
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL2425
IC50 7.1 6.5483 80.0 12
Dihydrofolate reductase
CHEMBL1075051
IC50 7.0 6.95 100.7 3
Toxoplasma gondii
CHEMBL612888
IC50 6.92 6.0553 120.0 15
ES1
CHEMBL2366146
IC50 6.91 6.91 122.9 1
Multidrug and toxin extrusion protein 1
CHEMBL3091264
Ki 6.84 6.84 145.0 1
Unchecked
CHEMBL612545
EC50 6.7 5.608 200.0 5
Toxoplasma gondii
CHEMBL612888
EC50 6.68 6.5083 210.0 6
Lacticaseibacillus casei
CHEMBL613075
IC50 6.62 5.955 240.0 2
Dihydrofolate reductase
CHEMBL202
IC50 6.4 5.5231 400.0 13
GR-ST
CHEMBL2366111
IC50 6.15 6.15 708.8 1
Respiratory syncytial virus
CHEMBL612679
EC50 6.12 6.12 750.0 1
LS-411N
CHEMBL2366189
IC50 6.08 6.08 836.8 1
ES8
CHEMBL2366069
IC50 6.05 6.05 896.7 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1163130
IC50 6.0 6.0 1000.0 1
Plasmodium cynomolgi
CHEMBL613883
IC50 5.99 5.99 1030.0 1
ALL-PO
CHEMBL2366294
IC50 5.93 5.93 1185.4 1
SK-NEP-1
CHEMBL1075580
IC50 5.91 5.91 1239.9 1
EW-1
CHEMBL2366364
IC50 5.86 5.86 1373.1 1
Dihydrofolate reductase
CHEMBL2363
IC50 5.85 5.697 1400.0 10
GI-ME-N
CHEMBL2366074
IC50 5.85 5.85 1402.7 1
NEC8
CHEMBL2366340
IC50 5.82 5.82 1501.7 1
ATN-1
CHEMBL2366277
IC50 5.75 5.75 1784.1 1
SCC-3
CHEMBL2366081
IC50 5.74 5.74 1841.3 1
Dihydrofolate reductase
CHEMBL1809
IC50 5.7 5.44 2000.0 2
Influenza B virus
CHEMBL613129
EC50 5.7 5.7 2000.0 1
J-RT3-T3-5
CHEMBL2366219
IC50 5.65 5.65 2219.2 1
ACN
CHEMBL2366195
IC50 5.64 5.64 2299.9 1
KM12
CHEMBL614709
IC50 5.63 5.63 2323.4 1
Dihydrofolate reductase
CHEMBL1926
IC50 5.62 5.495 2400.0 8
CMK
CHEMBL2366177
IC50 5.61 5.61 2460.3 1
CTV-1
CHEMBL2366360
IC50 5.61 5.61 2476.3 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL4296323
IC50 5.61 5.61 2480.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 5.6 5.3067 2510.0 3
ECC12
CHEMBL2366180
IC50 5.59 5.59 2561.8 1
SF-539
CHEMBL614860
IC50 5.59 5.59 2546.1 1

Pharmacokinetic Data

Parameter Value Units Species
CL 0.052 mL.min-1.kg-1 Homo sapiens
CL 8.6 mL.min-1.kg-1 Homo sapiens
Fu 0.095 - Homo sapiens
MRT 140.0 hr Homo sapiens
T1/2 140.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Plasmodium falciparum IC50 = 0.028 nM 10.55 Antimalarial activity against Plasmodium falciparum D6 infected in RBCs assessed... 20566761
Plasmodium falciparum IC50 = 0.055 nM 10.26 Antimalarial activity against Plasmodium falciparum D6 harboring Plasmodium viva... 20566761
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 0.19 nM 9.72 Inhibitor constant of compound for Plasmodium falciparum dihydrofolate reductase 1495020
Unchecked Ki = 0.59 nM 9.23 Binding affinity to wild type Plasmodium falciparum DHFR by competitive binding ... 20350951
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 0.6 nM 9.22 Inhibition of the wild-type dihydrofolate reductase (DHFR) 11881993
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 0.6 nM 9.22 Binding affinity towards wild-type dihydrofolate reductase of Plasmodium falcipa... 14736247
Unchecked Ki = 0.6 nM 9.22 Inhibition of Plasmodium falciparum TM4/8.2 wild type DHFR NCSI haplotype 30613332
Unchecked Ki = 0.6 nM 9.22 Competitive inhibition of wild type Plasmodium falciparum dihydrofolate reductas... 31685330
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 0.85 nM 9.07 Inhibition of pyrimethamine-resistant form-2 Plasmodium falciparum N51I, C59R, S... 17875995
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 0.87 nM 9.06 Inhibition constant against Plasmodium falciparum dihydrofolate reductase 15293997
Unchecked Ki = 1.07 nM 8.97 Inhibition of pyrimethamine-resistant form-3 Plasmodium falciparum N51I, C59R, S... 17875995
Plasmodium falciparum IC50 = 1.2 nM 8.92 In vitro inhibition of Plasmodium falciparum HB3 (S108N) culture 9554869
Dihydrofolate reductase Ki = 1.2 nM 8.92 Inhibitor constant of compound for mutant T46A Escherichia coli dihydrofolate re... 1495020
Unchecked Ki = 1.24 nM 8.91 Inhibition of pyrimethamine-resistant form-1 Plasmodium falciparum N51I, C59R, S... 17875995
Dihydrofolate reductase Kd = 1.4 nM 8.85 Thermodynamic dissociation constant of compound for mutant T46A Escherichia coli... 1495020
Plasmodium falciparum IC50 = 1.4 nM 8.85 Antimalarial activity against schizont stage of atovaquone-resistant Plasmodium ... -
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 1.4 nM 8.85 Inhibition constant against PfDHFR (Plasmodium falciparum dihydrofolate reductas... 12825927
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 1.5 nM 8.82 Binding affinity was evaluated as inhibition of recombinant wild type (WT) Plasm... 9554869
Dihydrofolate reductase Kd = 1.5 nM 8.82 Thermodynamic dissociation constant of compound for mutant T46S Escherichia coli... 1495020
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 1.5 nM 8.82 Inhibition constant against wild-type PfDHFR (Plasmodium falciparum dihydrofolat... 12825927

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 89
31158845 10.1038/s41586-019-1291-3 ADMET 67
17875995 10.1128/aac.00577-07 Unchecked 23
17237499 10.1074/jbc.m609304200 Beta-hexosaminidase subunit beta 18
18212105 10.1128/aac.01203-07 Toxoplasma gondii 17
28195463 10.1021/acs.jmedchem.6b01733 Plasmodium yoelii 16
17237499 10.1074/jbc.m609304200 Beta-hexosaminidase subunit alpha 15
28635296 10.1021/acs.jmedchem.7b00621 Plasmodium falciparum 14
20566761 10.1128/aac.00628-10 Plasmodium falciparum 14
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
32787140 10.1021/acs.jmedchem.0c00451 Plasmodium falciparum 13
1495020 10.1021/jm00093a026 Dihydrofolate reductase 12
102792 10.1021/jm00208a010 Plasmodium berghei 12
14736247 10.1021/jm030165t Bifunctional dihydrofolate reductase-thymidylate synthase 11
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
34666274 10.1016/j.bmc.2021.116467 Toxoplasma gondii 11
17371812 10.1128/aac.01607-06 Plasmodium falciparum 10
3881585 10.1021/jm00380a018 Mus musculus 10
7009867 10.1021/jm00134a002 Mus musculus 10
36274280 10.1016/j.ejmech.2022.114812 ADMET 9

Data from ChEMBL 36 via Core Engine