AntibioticMech

trimethoprim

CHEBI:45924 ·resolve ·ANTIBACTERIAL ·EXACT SEEDED

An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge. — ChEBI

Classification

diaminopyrimidine antibioticARO:3000171

Strictly broader compounds or drug classes this molecule belongs to.

• CHEBI:38338 CHEBI:38338
• CHEBI:51683 CHEBI:51683
• ARO:3000171 ARO:3000171

Chemical structure

Computed structure properties

Molecular formula	C14H18N4O3
Charge	0
Average mass	290.323 Da
Monoisotopic mass	290.13789 Da
Source	ChEBI
InChIKey	IEDVJHCEMCRBQM-UHFFFAOYSA-N

SMILES

COc1cc(Cc2cnc(N)nc2N)cc(OC)c1OC

InChI

InChI=1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18)

Also called

• 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine (EXACT_SYNONYM)— chebi
• 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine (EXACT_SYNONYM)— chebi
• 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine (EXACT_SYNONYM)— chebi
• Proloprim (EXACT_SYNONYM)— chebi
• TRIMETHOPRIM (EXACT_SYNONYM)— chebi
• Trimethoprim (EXACT_SYNONYM)— chebi
• Trimpex (EXACT_SYNONYM)— chebi

Cross-references

Equivalent identifiers for this same structure in other resources.

• ARO:3000188
• beilstein:625127
• cas:738-70-5
• drugbank:DB00440
• drugcentral:2755
• gmelin:808843
• hmdb:HMDB0014583
• kegg.compound:C01965
• kegg.drug:D00145
• lincs.smallmolecule:LSM-5246
• pdb-ccd:TOP
• reaxys:625127
• vsdb:1745
• wikipedia.en:Trimethoprim
• chembl:CHEMBL22
• pubchem.compound:5578

Activity roles

Every antimicrobial role a source asserts for this compound — the unreduced evidence behind its antimicrobial_class.

• CHEBI:36047 CHEBI:36047

Source concepts

Every upstream concept that resolved to this record. The merge is the product: this is what shows ChEBI and CARD are describing the same structure.

Upstream concepts merged into this record

Source	Native ID	Label	Minted CURIE	Version
ARO	ARO:3000188	trimethoprim	antibioticmech:aro-d69e4fcac6	2026-08-30
CHEBI	CHEBI:45924	trimethoprim	antibioticmech:chebi-5890ed9cd7	2026-08-30

Molecular targets

The molecular entity or process this compound acts on. Each target carries evidence — this is a mechanistic claim, not a classification.

antibiotic sensitive dihydrofolate reductase PROTEIN DIRECT_BINDING_TARGET

ARO:3000745

CARD/ARO database assertion; target organism, strain, and assay are not specified. Dihydrofolate reductase is asserted as the inhibited enzyme. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

• ARO:3000745 (CARD/ARO asserts targeted_by_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)

Dihydrofolate reductase PROTEIN MEASURED_TARGET_ASSOCIATION

BindingDB quantitative measurement in the named target organism; source assay descriptions and identifiers are retained per measurement. Evidence status: PRIMARY_EVIDENCE. Source: BINDINGDB 2026-09 (retrieved 2026-08-31).

Staphylococcus aureus NCBITaxon:1280

Quantitative measurements

Type	Reported value	Assay	BindingDB IDs	Reference
IC50	7 nM	Enzyme Inhibition Assay Activity was measured as a change in absorbance over time at a wavelength of 340 nm (A340), so as to monitor the disappearance of NADPH. After incubation of the enzyme with test compound and NADPH for 2 min, the reaction was initiated with the addition of DHF and the A340 was plotted over the course of 1.5 min. Six different concentrations of compound were utilized in the assays to determine the IC50.	RSID 32331 assay 2206_1 monomer 18069	PMID:14623005
IC50	23 nM	DHFR Inhibition Assay IC50 values were determined following a standard method that has been described previously (Reeve et al., 2014, 2016).	RSID 372397 assay 7681_1 monomer 18069	PMID:27939900
IC50	3.80e+5 nM	DHFR Inhibition Assay IC50 values were determined following a standard method that has been described previously (Reeve et al., 2014, 2016).	RSID 372406 assay 7681_1 monomer 18069	PMID:27939900

Organism-specific examples

Protein	Gene	Organism	Entry
Dihydrofolate reductase UniProtKB:P0A017	—	Staphylococcus aureus	REVIEWED
Dihydrofolate reductase UniProtKB:Q4H3Y3	—	Staphylococcus aureus	UNREVIEWED

• PMID:14623005 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)
• PMID:27939900 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)

Dihydrofolate reductase PROTEIN MEASURED_TARGET_ASSOCIATION

BindingDB quantitative measurement in the named target organism; source assay descriptions and identifiers are retained per measurement. Evidence status: PRIMARY_EVIDENCE. Source: BINDINGDB 2026-09 (retrieved 2026-08-31).

Bacillus anthracis NCBITaxon:1392

Quantitative measurements

Type	Reported value	Assay	BindingDB IDs	Reference
IC50	77300 nM	Enzyme Inhibition Assay Activity was measured as a change in absorbance over time at a wavelength of 340 nm (A340), so as to monitor the disappearance of NADPH. After incubation of the enzyme with test compound and NADPH for 3 min, the reaction was initiated with the addition of DHF and the A340 was plotted over the course of 3 min. Six different concentrations of compound were utilized in the assays to determine the IC50.	RSID 32320 assay 2205_1 monomer 18069	PMID:15561838
IC50	71000 nM	Enzyme Inhibition Assay Enzyme activity assays were performed by monitoring the rate of enzyme-dependent NADPH oxidation at an absorbance of 340 nm over several minutes. All enzyme assays were performed with a single, limiting concentration of enzyme and saturating concentrations of NADPH and dihydrofolate. IC50 values were calculated as the average of three independent experiments.	RSID 48413 assay 2975_1 monomer 18069	PMID:19007108

Organism-specific examples

Protein	Gene	Organism	Entry
Dihydrofolate reductase UniProtKB:Q81R22	—	Bacillus anthracis	UNREVIEWED

• PMID:15561838 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)
• PMID:19007108 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)

Dihydrofolate reductase PROTEIN MEASURED_TARGET_ASSOCIATION

BindingDB quantitative measurement in the named target organism; source assay descriptions and identifiers are retained per measurement. Evidence status: PRIMARY_EVIDENCE. Source: BINDINGDB 2026-09 (retrieved 2026-08-31).

Mycobacterium avium NCBITaxon:1764

Quantitative measurements

Type	Reported value	Assay	BindingDB IDs	Reference
IC50	5750 nM	Enzyme Inhibition Assay Activity was measured as a change in absorbance over time at a wavelength of 340 nm (A340), so as to monitor the disappearance of NADPH. After incubation of the enzyme with test compound and NADPH for 3 min, the reaction was initiated with the addition of DHF and the A340 was plotted over the course of 3 min. Six different concentrations of compound were utilized in the assays to determine the IC50.	RSID 32322 assay 2205_1 monomer 18069	PMID:15561838
IC50	300 nM	Determination of IC50 Dihydrofolate reductase was assayed with no inhibitor and with a series of concentrations of inhibitors to allow for a range of inhibition from 10 to 90%. At least three concentrations were required for calculation. Semilogarithmic plots of the data showed a normal sigmoidal plot for most inhibitors. These plots were converted to straight lines by converting percent inhibition to probit values which were plotted versus the log of the drug concentration. The data were fit by least-squares linear regression. The 50% inhibitory concentration (IC50) is the concentration at which the probit value is 5.0.	RSID 32561 assay 2221_1 monomer 18069	PMID:15974594
IC50	300 nM	Dihydrofolate Reductase (DHFR) Assay Enzymatic activities were determined by monitoring the oxidation of NADPH at 340 nm using a 96-well microtiter plate reading spectrophotometer.	RSID 32711 assay 2225_1 monomer 18069	PMID:17552508

Organism-specific examples

Protein	Gene	Organism	Entry
Dihydrofolate reductase UniProtKB:O30463	—	Mycobacterium avium	UNREVIEWED

• PMID:15561838 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)
• PMID:15974594 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)
• PMID:17552508 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)

Dihydrofolate reductase PROTEIN MEASURED_TARGET_ASSOCIATION

BindingDB quantitative measurement in the named target organism; source assay descriptions and identifiers are retained per measurement. Evidence status: PRIMARY_EVIDENCE. Source: BINDINGDB 2026-09 (retrieved 2026-08-31).

Pneumocystis carinii NCBITaxon:4754

Quantitative measurements

Type	Reported value	Assay	BindingDB IDs	Reference
IC50	43000 nM	Enzyme Inhibition Assay Activity was measured as a change in absorbance over time at a wavelength of 340 nm (A340), so as to monitor the disappearance of NADPH. After incubation of the enzyme with test compound and NADPH for 2 min, the reaction was initiated with the addition of DHF and the A340 was plotted over the course of 1.5 min. Six different concentrations of compound were utilized in the assays to determine the IC50.	RSID 32335 assay 2206_1 monomer 18069	PMID:14623005
IC50	13000 nM	Determination of IC50 Dihydrofolate reductase was assayed with no inhibitor and with a series of concentrations of inhibitors to allow for a range of inhibition from 10 to 90%. At least three concentrations were required for calculation. Semilogarithmic plots of the data showed a normal sigmoidal plot for most inhibitors. These plots were converted to straight lines by converting percent inhibition to probit values which were plotted versus the log of the drug concentration. The data were fit by least-squares linear regression. The 50% inhibitory concentration (IC50) is the concentration at which the probit value is 5.0.	RSID 32515 assay 2221_1 monomer 18069	PMID:15974594
IC50	12000 nM	Dihydrofolate Reductase (DHFR) Assay Enzymatic activities were determined by monitoring the oxidation of NADPH at 340 nm using a 96-well microtiter plate reading spectrophotometer.	RSID 32665 assay 2225_1 monomer 18069	PMID:17552508

Organism-specific examples

Protein	Gene	Organism	Entry
Dihydrofolate reductase UniProtKB:P16184	—	Pneumocystis carinii	REVIEWED

• PMID:14623005 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)
• PMID:15974594 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)
• PMID:17552508 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)

Dihydrofolate reductase type 1 from Tn4003 PROTEIN MEASURED_TARGET_ASSOCIATION

BindingDB quantitative measurement in the named target organism; source assay descriptions and identifiers are retained per measurement. Evidence status: PRIMARY_EVIDENCE. Source: BINDINGDB 2026-09 (retrieved 2026-08-31).

Staphylococcus aureus NCBITaxon:1280

Quantitative measurements

Type	Reported value	Assay	BindingDB IDs	Reference
IC50	1.51e+4 nM	DHFR Inhibition Assay IC50 values were determined following a standard method that has been described previously (Reeve et al., 2014, 2016).	RSID 372415 assay 7681_1 monomer 18069	PMID:27939900

Organism-specific examples

Protein	Gene	Organism	Entry
Dihydrofolate reductase type 1 from Tn4003 UniProtKB:P13955	—	Staphylococcus aureus	REVIEWED

• PMID:27939900 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)

Mechanism summary

Mode of action

FOLATE_PATHWAY_INHIBITION host shared target — Assigned from ChEBI role CHEBI:50683 (EC 1.5.1.3 (dihydrofolate reductase) inhibitor). ChEBI asserts the role on the compound. The target it names is one the host has too, so the mechanism is true but is not evidence of selectivity — see mode_of_action_target_scope. Not a curator's mechanistic review.

Clinical status

APPROVED

Resistance mechanisms

69 known routes by which microbes resist this compound, grounded in ARO where CARD models them. Grouped by mechanism type — expand a group to see its determinants.

ANTIBIOTIC_TARGET_REPLACEMENT 60

ANTIBIOTIC_TARGET_REPLACEMENT

Determinant	ARO ID	Organism	Gene families	Evidence
DfrA34	ARO:3005346	not organism-specific	—	ARO:3005346 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
DfrA36	ARO:3005348	not organism-specific	—	ARO:3005348 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
DfrA37	ARO:3005347	not organism-specific	—	ARO:3005347 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
DfrA38	ARO:3005349	not organism-specific	—	ARO:3005349 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
DfrA39	ARO:3005351	not organism-specific	—	ARO:3005351 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
DfrB9	ARO:3005350	not organism-specific	—	ARO:3005350 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
Trimethoprim-resistant dihydrofolate reductase DfrA42	ARO:3005334	not organism-specific	—	ARO:3005334 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
Trimethoprim-resistant dihydrofolate reductase DfrA43	ARO:3005345	not organism-specific	—	ARO:3005345 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfr22	ARO:3005354	not organism-specific	—	ARO:3005354 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA1	ARO:3002854	not organism-specific	—	ARO:3002854 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA10	ARO:3003011	not organism-specific	—	ARO:3003011 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA12	ARO:3002858	not organism-specific	—	ARO:3002858 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA13	ARO:3003012	not organism-specific	—	ARO:3003012 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA14	ARO:3002859	not organism-specific	—	ARO:3002859 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA15	ARO:3003013	not organism-specific	—	ARO:3003013 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA15b	ARO:3004640	not organism-specific	—	ARO:3004640 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA16	ARO:3003014	not organism-specific	—	ARO:3003014 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA17	ARO:3002860	not organism-specific	—	ARO:3002860 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA18	ARO:3004568	not organism-specific	—	ARO:3004568 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA19	ARO:3003015	not organism-specific	—	ARO:3003015 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA20	ARO:3003016	not organism-specific	—	ARO:3003016 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA21	ARO:3003017	not organism-specific	—	ARO:3003017 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA22	ARO:3003018	not organism-specific	—	ARO:3003018 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA23	ARO:3003019	not organism-specific	—	ARO:3003019 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA24	ARO:3002856	not organism-specific	—	ARO:3002856 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA25	ARO:3003020	not organism-specific	—	ARO:3003020 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA26	ARO:3002857	not organism-specific	—	ARO:3002857 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA27	ARO:3004550	not organism-specific	—	ARO:3004550 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA28	ARO:3004551	not organism-specific	—	ARO:3004551 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA29	ARO:3004554	not organism-specific	—	ARO:3004554 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA3	ARO:3003105	not organism-specific	—	ARO:3003105 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA30	ARO:3004552	not organism-specific	—	ARO:3004552 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA31	ARO:3005084	not organism-specific	—	ARO:3005084 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA32	ARO:3004555	not organism-specific	—	ARO:3004555 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA35	ARO:3005164	not organism-specific	—	ARO:3005164 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA3b	ARO:3004642	not organism-specific	—	ARO:3004642 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA5	ARO:3002861	not organism-specific	—	ARO:3002861 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA6	ARO:3004547	not organism-specific	—	ARO:3004547 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA6 from Proteus mirabilis	ARO:3004644	not organism-specific	—	ARO:3004644 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA7	ARO:3002862	not organism-specific	—	ARO:3002862 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA8	ARO:3002863	not organism-specific	—	ARO:3002863 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrA9	ARO:3004548	not organism-specific	—	ARO:3004548 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB1	ARO:3002864	not organism-specific	—	ARO:3002864 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB10	ARO:3007489	not organism-specific	—	ARO:3007489 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB11	ARO:3007490	not organism-specific	—	ARO:3007490 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB2	ARO:3003021	not organism-specific	—	ARO:3003021 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB3	ARO:3003022	not organism-specific	—	ARO:3003022 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB4	ARO:3004498	not organism-specific	—	ARO:3004498 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB5	ARO:3004549	not organism-specific	—	ARO:3004549 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB6	ARO:3003023	not organism-specific	—	ARO:3003023 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrB7	ARO:3004556	not organism-specific	—	ARO:3004556 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrC	ARO:3002865	not organism-specific	—	ARO:3002865 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrD	ARO:3002866	not organism-specific	—	ARO:3002866 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrE	ARO:3002875	not organism-specific	—	ARO:3002875 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrF	ARO:3002867	not organism-specific	—	ARO:3002867 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrG	ARO:3002868	not organism-specific	—	ARO:3002868 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrI	ARO:3004645	not organism-specific	—	ARO:3004645 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrK	ARO:3002869	not organism-specific	—	ARO:3002869 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
dfrL	ARO:3007456	not organism-specific	—	ARO:3007456 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
trimethoprim resistant dihydrofolate reductase dfr	ARO:3001218	not organism-specific	—	ARO:3001218 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)

ANTIBIOTIC_EFFLUX 9

ANTIBIOTIC_EFFLUX

Determinant	ARO ID	Organism	Gene families	Evidence
AdeIJK	ARO:3000772	not organism-specific	—	ARO:3000772 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
MexAB-OprM	ARO:3000386	not organism-specific	—	ARO:3000386 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
MexCD-OprJ	ARO:3000797	not organism-specific	—	ARO:3000797 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
MexEF-OprN	ARO:3000798	not organism-specific	—	ARO:3000798 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
MexEF-OprN with MexS mutations conferring resistance to chloramphenicol, ciprofloxacin, and trimethoprim	ARO:3004068	not organism-specific	—	ARO:3004068 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
MexEF-OprN with MexT mutation conferring resistance to chloramphenicol, ciprofloxacin, and trimethoprim	ARO:3004066	not organism-specific	—	ARO:3004066 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
MexPQ-OpmE	ARO:3003697	not organism-specific	—	ARO:3003697 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
Staphylococcus aureus LmrS	ARO:3004572	not organism-specific	—	ARO:3004572 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)
oqxAB	ARO:3003921	not organism-specific	—	ARO:3003921 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000188 (trimethoprim); database assertion, not a primary citation.)

Causal graphs

Evidence-backed mechanism graphs: how the compound reaches its target, what the target does, and how the effect propagates to growth inhibition or death.

Trimethoprim inhibits bacterial dihydrofolate reductase MECHANISTIC

Trimethoprim inhibits bacterial dihydrofolate reductase, reducing tetrahydrofolate regeneration and one-carbon transfer reactions needed for nucleotide biosynthesis and growth.

Nodes — trimethoprim_folate_pathway_inhibition

Node	Label	Type	Grounding
trimethoprim	trimethoprim	COMPOUND	CHEBI:45924
bacterial_dhfr	antibiotic-sensitive dihydrofolate reductase	GENE_OR_PROTEIN	ARO:3000745
dhfr_activity	dihydrofolate reductase activity	MOLECULAR_FUNCTION	GO:0004146
reduced_folate_pool	reduced folate pool	STATE	REVIEWED_LABEL_ONLY
nucleotide_biosynthesis	folate-dependent nucleotide biosynthesis	BIOLOGICAL_PROCESS	REVIEWED_LABEL_ONLY
bacterial_growth	bacterial growth	BIOLOGICAL_PROCESS	REVIEWED_LABEL_ONLY

Edges — trimethoprim_folate_pathway_inhibition

Subject	Predicate	Object	Evidence
trimethoprim	inhibits	bacterial_dhfr	PMID:14623005 (BindingDB-curated Staphylococcus aureus DHFR IC50 measurements in this record support direct enzyme inhibition by trimethoprim.)
bacterial_dhfr	enables	dhfr_activity	PMID:4254117 (Miovic and Pizer treated Escherichia coli with trimethoprim to connect DHFR inhibition to folate-dependent macromolecular synthesis defects.)
dhfr_activity	maintains	reduced_folate_pool	PMID:4254117 (Primary E. coli trimethoprim experiments support reduced folate regeneration as the metabolic step downstream of DHFR.)
reduced_folate_pool	supplies one-carbon cofactors for	nucleotide_biosynthesis	PMID:4254117 (Primary E. coli trimethoprim experiments support nucleotide biosynthesis as a downstream consequence of DHFR inhibition.)
nucleotide_biosynthesis	supports	bacterial_growth	PMID:4254117 (Macromolecular-synthesis phenotypes in trimethoprim-treated E. coli connect DHFR inhibition to growth arrest.)

Curation history

1. SEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources

   Seeded from data/raw/ inventories (ARO, CHEBI)

2. RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources

   Re-seeded from updated data/raw/ inventories

3. RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources

   Re-seeded from updated data/raw/ inventories

4. RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources

   Re-seeded from updated data/raw/ inventories

5. RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources

   Re-seeded from updated data/raw/ inventories

6. RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources

   Re-seeded from updated data/raw/ inventories

7. RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources

   Re-seeded from updated data/raw/ inventories

8. CURATED_CAUSAL_GRAPH 2026-09-04 · codex · LLM-assisted

   Added a PMID-supported causal graph for trimethoprim inhibition of bacterial dihydrofolate reductase and downstream folate-dependent nucleotide biosynthesis.

Provenance

Seeded by scripts/seed_from_sources.py from the committed inventories in data/raw/. View the record.