Trimetrexate

Summary

Trimetrexate (CHEMBL119) is an approved small molecule (ATC P01AX07) targeting DHFR; indicated across 1 condition including amebiasis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: P01AX07
• Targets: 1 (DHFR)
• Indications: 1 condition
• Chemistry: 369.4 Da · C19H23N5O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL119
Name	Trimetrexate
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	5583
ATC	P01AX07
Molecular formula	C19H23N5O3
Molecular weight	369.4
InChIKey	NOYPYLRCIDNJJB-UHFFFAOYSA-N

SMILES: CC1=C(C=CC2=C1C(=NC(=N2)N)N)CNC3=CC(=C(C(=C3)OC)OC)OC

IUPAC name: 5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine

Also known as: CI-898, NSC-249008, Trimetrexate, Trimetrexato, trimetrexate, SID26755046, SID50110873, TRIMETREXATE, C0088486

Parent form; salt/anhydrous children: CHEMBL2218878, CHEMBL2358886, CHEMBL3392303

Patent coverage: 13,389 distinct patent families (57,002 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 56,872 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DHFR	dihydrofolate reductase	Inhibition	7.89	69.8%	P00374

Broader ChEMBL bioactivity targets: 33 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Bifunctional dihydrofolate reductase-thymidylate synthase, Microtubule-associated protein tau, Fructose-bisphosphate aldolase, RecQ-like DNA helicase BLM, 4’-phosphopantetheinyl transferase ffp, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Dihydrofolate reductase, Dihydrofolate reductase, Amine oxidase [flavin-containing] A.

Bioactivity

ChEMBL activities: 144 potent at pChembl ≥ 5 of 160 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DHFR	10.4	Ki	0.04	nM	CHEMBL_ACT_24959142
P00375	10.22	Ki	0.06	nM	CHEMBL_ACT_654949
DHFR	9.38	IC50	0.42	nM	CHEMBL_ACT_24999756
P16184	9.15	Ki	0.71	nM	CHEMBL_ACT_95459
P00375	9.09	Ki	0.81	nM	CHEMBL_ACT_654950
Q07422	8.87	IC50	1.35	nM	CHEMBL_ACT_19365587
DHFR	8.85	IC50	1.4	nM	CHEMBL_ACT_220405
DHFR	8.85	Ki	1.4	nM	CHEMBL_ACT_576794
P22906	8.72	Ki	1.9	nM	CHEMBL_ACT_576793
DHFR	8.59	IC50	2.6	nM	CHEMBL_ACT_13297381
DHFR	8.59	IC50	2.6	nM	CHEMBL_ACT_19192953
DHFR	8.59	IC50	2.6	nM	CHEMBL_ACT_28502444
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1015010
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1050231
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1068772
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1090497
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1119202
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1122911
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1176310
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1224427
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_1258099
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_13297297
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_172639
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_202736
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_220404
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_227040
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_2361856
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_237267
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_2559435
Q920D2	8.52	IC50	3	nM	CHEMBL_ACT_3106726

Target pathways

Aggregated over 1 target gene(s): DHFR.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	1	DHFR
Metabolism of folate and pterines	1	DHFR
G1/S-Specific Transcription	1	DHFR

Dominant GO biological processes

GO term	Targets
tetrahydrobiopterin biosynthetic process	1
one-carbon metabolic process	1
negative regulation of translation	1
axon regeneration	1
response to methotrexate	1
dihydrofolate metabolic process	1
tetrahydrofolate metabolic process	1
tetrahydrofolate biosynthetic process	1
folic acid metabolic process	1
regulation of removal of superoxide radicals	1

Indications & clinical

Indications

1 indication (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
amebiasis	2	MONDO:0005644	EFO:0007144

Clinical trials

Total trials: 0.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

22 molecules share ≥1 primary target. Top 22 by shared-target count:

Molecule	Source	Status	Shared targets
LEUCOVORIN	ChEMBL + PubChem	Phase 4 (approved)	DHFR
METHOTREXATE	ChEMBL + PubChem	Phase 4 (approved)	DHFR
PEMETREXED	ChEMBL + PubChem	Phase 4 (approved)	DHFR
DIFLUNISAL	ChEMBL	Phase 4 (approved)	DHFR
GENTAMICIN	ChEMBL	Phase 4 (approved)	DHFR
MEFENAMIC ACID	ChEMBL	Phase 4 (approved)	DHFR
PRALATREXATE	ChEMBL	Phase 4 (approved)	DHFR
PYRIMETHAMINE	ChEMBL	Phase 4 (approved)	DHFR
RALTITREXED	ChEMBL	Phase 4 (approved)	DHFR
SULFACETAMIDE	ChEMBL	Phase 4 (approved)	DHFR
SULFADIAZINE	ChEMBL	Phase 4 (approved)	DHFR
TERIFLUNOMIDE	ChEMBL	Phase 4 (approved)	DHFR
TRIMETHOPRIM	ChEMBL	Phase 4 (approved)	DHFR
ICLAPRIM	ChEMBL	Phase 3	DHFR
AMINOPTERIN	ChEMBL	Phase 2	DHFR
BREQUINAR	ChEMBL	Phase 2	DHFR
CYCLOGUANIL	ChEMBL	Phase 2	DHFR
DIAVERIDINE	ChEMBL	Phase 2	DHFR
EDATREXATE	ChEMBL	Phase 2	DHFR
EPIROPRIM	ChEMBL	Phase 2	DHFR
PIRITREXIM	ChEMBL	Phase 2	DHFR
Folic Acid	PubChem	Approved	DHFR