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Compound Detail

CHEMBL22

TRIMETHOPRIM
💊 Approved Drug
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💊 Approved Drug
COc1cc(Cc2cnc(N)nc2N)cc(OC)c1OC
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL22
Name TRIMETHOPRIM
Phase Approved
Structure Type MOL
InChI Key IEDVJHCEMCRBQM-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

BW 56-72 BW-56-72 Infectotrimet Ipral Ledatrim Monotrim NIH-204 NSC-106568 Proloprim Proloprin Syraprim TCMDC-125538 +18 more
34
Targets
433
Activities
3
Assay Types
22
PK Parameters
20
Publications
30
Known Names
20
Indications
1
Mechanisms

Molecular Properties

290.3
MW (Da)
1.26
ALogP
7
HBA
2
HBD
105.5
PSA (Ų)
0.85
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1973
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Parenteral Topical

Flags

Natural Product
USAN Stem -prim
USAN Year 1964

Extended Properties

Molecular Formula C14H18N4O3
MW 290.32
Aromatic Rings 2
Heavy Atoms 21
NP-Likeness 0.07

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Bacterial dihydrofolate reductase inhibitor INHIBITOR Dihydrofolate reductase ✓ ✓

Indications

Bacterial Infections Infections Otitis Media Pneumonia, Pneumocystis Urinary Tract Infections Abscess HIV Infections Idiopathic Pulmonary Fibrosis Malaria Measles Pneumonia Pyelonephritis Sepsis Staphylococcal Infections Toxoplasmosis, Ocular Tuberculosis Cystic Fibrosis Dermatitis Diabetes Mellitus, Type 1 Eczema

ATC Classification

J01EA01
trimethoprim
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIBACTERIALS FOR SYSTEMIC USE

Activity Summary

IC50 362 meas. best 10.85
Ki 70 meas. best 10.7
Kd 1 meas. best 8.06

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Unchecked
CHEMBL612545
 IC50 10.85 6.5297 0.0 32
Unchecked
CHEMBL612545
 Ki 10.7 7.1807 0.0 15
Dihydrofolate reductase
CHEMBL1809
 Ki 9.66 8.93 0.2 7
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1939
 Ki 9.23 6.97 0.6 8
Dihydrofolate reductase
CHEMBL1681620
 Ki 8.92 7.7162 1.2 13
Dihydrofolate reductase
CHEMBL2329
 IC50 8.66 5.47 2.2 6
Dihydrofolate reductase
CHEMBL1809
 IC50 8.3 7.6778 5.0 23
Dihydrofolate reductase
CHEMBL1681620
 IC50 8.15 6.488 7.0 10
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL2425
 IC50 8.14 5.5413 7.2 40
Dihydrofolate reductase
CHEMBL4888
 Ki 8.08 8.08 8.3 2
Unchecked
CHEMBL612545
 Kd 8.06 8.06 8.7 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL1939
 IC50 8.0 8.0 10.0 1
Dihydrofolate reductase
CHEMBL202
 Ki 8.0 5.9 10.0 11
Lacticaseibacillus casei
CHEMBL613075
 IC50 7.77 7.16 17.0 3
Dihydrofolate reductase
CHEMBL1926
 IC50 7.34 4.9419 46.0 36
Dihydrofolate reductase
CHEMBL2902
 IC50 7.27 6.67 54.0 4
Dihydrofolate reductase
CHEMBL202
 IC50 7.27 5.7265 54.0 20
Enterococcus faecium
CHEMBL357
 IC50 7.1 6.51 80.0 2
Dihydrofolate reductase
CHEMBL2057
 IC50 7.04 7.04 92.0 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL4614
 Ki 6.92 6.92 120.0 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL3963
 IC50 6.92 6.92 120.0 5
Dihydrofolate reductase
CHEMBL2902
 Ki 6.88 6.88 131.8 1
Dihydrofolate reductase
CHEMBL1926
 Ki 6.82 6.82 151.4 2
Dihydrofolate reductase
CHEMBL5457
 IC50 6.72 6.595 190.0 8
Bacillus subtilis
CHEMBL359
 IC50 6.52 6.52 300.0 1
Plasmodium falciparum
CHEMBL364
 IC50 6.42 5.0941 380.2 49
Escherichia coli
CHEMBL354
 IC50 6.4 6.4 400.0 1
Dihydrofolate reductase
CHEMBL2364669
 IC50 6.35 5.635 450.0 2
Dihydrofolate reductase
CHEMBL4012
 IC50 6.35 6.35 450.0 1
Dihydrofolate reductase
CHEMBL3565
 IC50 6.35 6.35 450.0 2
Dihydrofolate reductase
CHEMBL5270
 Ki 6.32 5.2667 480.0 3
Dihydrofolate reductase
CHEMBL4564
 Ki 6.3 6.3 500.0 1
Dihydrofolate reductase type 1
CHEMBL2627
 IC50 6.3 6.3 500.0 1
Dihydrofolate reductase
CHEMBL5270
 IC50 5.42 4.614 3780.0 5
Cryptosporidium parvum
CHEMBL612855
 IC50 5.4 5.4 4000.0 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL2366489
 IC50 5.4 5.125 4000.0 2
NON-PROTEIN TARGET
CHEMBL3879801
 IC50 4.93 4.55 11700.0 2
Dihydrofolate reductase
CHEMBL2576
 IC50 4.92 4.92 12000.0 1
Toxoplasma gondii
CHEMBL612888
 IC50 4.89 4.574 13000.0 5
Dihydrofolate reductase
CHEMBL2363
 Ki 4.84 4.84 14300.0 1
Bifunctional dihydrofolate reductase-thymidylate synthase
CHEMBL4614
 IC50 4.69 4.69 20500.0 1
Dihydrofolate reductase
CHEMBL2363
 IC50 4.47 4.435 34000.0 2
Dihydrofolate reductase
CHEMBL4296314
 IC50 4.38 4.38 42000.0 1
Solute carrier family 22 member 1
CHEMBL5685
 IC50 4.29 4.27 50680.0 2
Dihydrofolate reductase
CHEMBL6065
 IC50 4.06 4.06 88000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 2.1 mL.min-1.kg-1 Homo sapiens
CL 1.2 mL.min-1.kg-1 Homo sapiens
CL 2.1 mL.min-1.kg-1 Homo sapiens
CL 2.1 mL.min-1.kg-1 Homo sapiens
CL 3.0 mL.min-1.g-1 Homo sapiens
CL 8.6 mL.min-1.kg-1 Homo sapiens
Cmax 7922.29 nM Homo sapiens
F 99.0 % Canis lupus familiaris
F 80.0 % Homo sapiens
F 63.0 % Homo sapiens
F 98.0 % Homo sapiens
Fu 0.63 - -
Fu 0.166 - -
Fu 0.63 - Homo sapiens
Fu 0.5 - Homo sapiens
Fu 0.5 - Homo sapiens
MRT 12.0 hr Homo sapiens
T1/2 3.44 hr Canis lupus familiaris
T1/2 0.76 hr Mus musculus
T1/2 2.7 hr Mus musculus
T1/2 2.01 hr Oryctolagus cuniculus
T1/2 9.6 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked IC50 = 0.014 nM 10.85 Inhibition of recombinant Staphylococcus aureus His-tagged DHFR using DiHF as su... 34046602
Unchecked IC50 = 0.02 nM 10.7 Inhibition of recombinant Escherichia coli DHFR expressed in Escherichia coli BL... 34046602
Unchecked Ki = 0.02 nM 10.7 Inhibition of Escherichia coli chromosomal Dfr 33214838
Unchecked Ki = 0.19 nM 9.72 Inhibition of Haemophilus influenzae DHFR assessed as oxidation of NADPH using d... 21831637
Unchecked Ki = 0.2 nM 9.7 Inhibition of recombinant Escherichia coli DHFR expressed in Escherichia coli BL... 34046602
Dihydrofolate reductase Ki = 0.22 nM 9.66 Inhibition of recombinant Escherichia coli DHFR expressed in Escherichia coli BL... 27437079
Bifunctional dihydrofolate reductase-thymidylate synthase Ki = 0.59 nM 9.23 Inhibition of wild type Plasmodium falciparum DHFR using DHF as substrate assess... 37731689
Unchecked IC50 = 1.0 nM 9.0 Inhibition of Escherichia coli DHFR preincubated with NADPH for 3 mins followed ... 35258959
Dihydrofolate reductase Ki = 1.2 nM 8.92 Inhibition of Staphylococcus aureus DHFR using dihydrofolate as substrate preinc... 24428639
Dihydrofolate reductase Ki = 1.24 nM 8.91 Inhibition of Staphylococcus aureus DHFR assessed as oxidation of NADPH using di... 21831637
Dihydrofolate reductase Ki = 1.3 nM 8.89 Apparent binding affinity against Dihydrofolate reductase in Escherichia coli 2666668
Dihydrofolate reductase Ki = 1.3 nM 8.89 Binding affinity against Dihydrofolate reductase of Escherichia coli 3973902
Dihydrofolate reductase Ki = 1.3 nM 8.89 Antibacterial activity against Escherichia coli 2754716
Dihydrofolate reductase Ki = 1.3 nM 8.89 Binding affinity for Escherichia coli Dihydrofolate reductase 6754932
Dihydrofolate reductase Ki = 1.349 nM 8.87 Inhibition constant against binding of Escherichia coli dihydrofolate reductase 3290487
Unchecked IC50 = 1.5 nM 8.82 Inhibition of Mycobacterium avium DHFR 23627352
Dihydrofolate reductase IC50 = 2.2 nM 8.66 Inhibitory activity against cell free dihydrofolate reductase (DHFR) from Escher... 14695838
Dihydrofolate reductase Ki = 3.43 nM 8.46 Inhibition of TMP/methicillin-resistant Staphylococcus aureus wild type DHFR ass... 27308944
Dihydrofolate reductase Ki = 3.43 nM 8.46 Inhibition of recombinant Staphylococcus aureus DHFR expressed in Escherichia co... 27437079
Dihydrofolate reductase Ki = 3.8 nM 8.42 Inhibition constant against Dihydrofolate reductase 12852950

Literature References

PubMed DOI Target Context # Activities
19734910 10.1038/nchembio.215 Plasmodium falciparum 46
19289528 10.1128/aac.00129-09 Staphylococcus aureus 36
19188385 10.1128/aac.01619-08 Staphylococcus aureus 35
26979156 10.1016/j.bmcl.2016.03.015 NON-PROTEIN TARGET 33
19114678 10.1128/aac.01260-08 NON-PROTEIN TARGET 20
17420206 10.1128/aac.00052-07 Escherichia coli 20
18070962 10.1128/aac.00375-07 Escherichia coli 19
18180352 10.1128/aac.01094-07 Proteus mirabilis 19
19289528 10.1128/aac.00129-09 Enterococcus faecalis 18
29784273 10.1016/j.bmc.2018.05.019 Staphylococcus aureus 18
19289528 10.1128/aac.00129-09 Enterococcus faecium 18
19289528 10.1128/aac.00129-09 Streptococcus sp. 'group A' 17
37698518 10.1021/acs.jmedchem.3c00891 Staphylococcus aureus 17
19289528 10.1128/aac.00129-09 Streptococcus sp. 'group B' 17
19738027 10.1128/aac.00845-09 Staphylococcus aureus 16
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
24428639 10.1021/jm401204g Streptococcus pneumoniae 12
7035668 10.1021/jm00140a005 Mus musculus 12
12773035 10.1021/jm020495y Dihydrofolate reductase 11
19546364 10.1128/aac.00377-09 Staphylococcus aureus 11

Data from ChEMBL 36 via Core Engine