Raltitrexed

Summary

Raltitrexed (CHEMBL225071) is an approved small molecule (ATC L01BA03) targeting TYMS; indicated across 17 conditions including neoplasm and mesothelioma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01BA03
• Targets: 1 (TYMS)
• Indications: 17 conditions
• Clinical trials: 40
• Chemistry: 458.5 Da · C21H22N4O6S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL225071
Name	Raltitrexed
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	135400182
ATC	L01BA03
Molecular formula	C21H22N4O6S
Molecular weight	458.5
InChIKey	IVTVGDXNLFLDRM-HNNXBMFYSA-N

SMILES: CC1=NC2=C(C=C(C=C2)CN(C)C3=CC=C(S3)C(=O)N[C@@H](CCC(=O)O)C(=O)O)C(=O)N1

IUPAC name: (2S)-2-[[5-[methyl-[(2-methyl-4-oxo-3H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid

Also known as: Raltitrexed, Tomudex, ZD-16, ZD-1694, ZD1694, raltitrexed, SID49681782, SID499545, RALTITREXED, SID144205790, SID144207198, RALTITREXED (TOMUDEX)

Patent coverage: 22,950 distinct patent families (96,748 SureChEMBL compound mentions), from 4 matched compound structure(s). 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
TYMS	thymidylate synthetase	Inhibition	6.54	50.8%	P04818

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Proton-coupled folate transporter, Dihydrofolate reductase, Thymidylate synthase, Dihydrofolate reductase, Folate receptor alpha, Bifunctional dihydrofolate reductase-thymidylate synthase, Thymidylate synthase, Thymidylate synthase, Thymidylate synthase, Reduced folate transporter.

Bioactivity

ChEMBL activities: 42 potent at pChembl ≥ 5 of 47 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC19A1	8.2	IC50	6.3	nM	CHEMBL_ACT_15072136
SLC19A1	8.2	IC50	6.3	nM	CHEMBL_ACT_18527732
DHFR	8.05	IC50	9	nM	CHEMBL_ACT_24959146
TYMS	8.05	IC50	9	nM	CHEMBL_ACT_24959147
FOLR1	7.82	IC50	15	nM	CHEMBL_ACT_15072118
FOLR1	7.82	IC50	15	nM	CHEMBL_ACT_18527754
FOLR2	7.66	IC50	22	nM	CHEMBL_ACT_15072100
FOLR2	7.66	IC50	22	nM	CHEMBL_ACT_18527776
SLC46A1	7	IC50	99.5	nM	CHEMBL_ACT_15067596
SLC46A1	7	IC50	99.5	nM	CHEMBL_ACT_18527798
EHMT2	6.92	IC50	120	nM	CHEMBL_ACT_25729360
TYMS	6.58	IC50	260	nM	CHEMBL_ACT_13314008
TYMS	6.54	IC50	290	nM	CHEMBL_ACT_10944983
TYMS	6.54	IC50	290	nM	CHEMBL_ACT_3242725
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_12729415
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_1519636
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_1676861
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_18029918
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_1842425
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_1845048
TYMS	6.42	IC50	380	nM	CHEMBL_ACT_3106780
P07607	6.38	Ki	418	nM	CHEMBL_ACT_870109
Q07422	6.32	IC50	480	nM	CHEMBL_ACT_10945892
TYMS	6.28	IC50	530	nM	CHEMBL_ACT_153649
TYMS	6.17	IC50	676.1	nM	CHEMBL_ACT_3268689
P07607	6.17	IC50	670	nM	CHEMBL_ACT_479346
P07607	6.17	IC50	670	nM	CHEMBL_ACT_99597
FOLR2	6.13	IC50	746	nM	CHEMBL_ACT_15067605
FOLR2	6.13	IC50	746	nM	CHEMBL_ACT_18527787
TYMS	6.06	IC50	880	nM	CHEMBL_ACT_153645

Target pathways

Aggregated over 1 target gene(s): TYMS.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Interconversion of nucleotide di- and triphosphates	1	TYMS
G1/S-Specific Transcription	1	TYMS

Dominant GO biological processes

GO term	Targets
dTMP biosynthetic process	1
dTTP biosynthetic process	1
negative regulation of translation	1
methylation	1
tetrahydrofolate interconversion	1
DNA biosynthetic process	1
one-carbon metabolic process	1
nucleotide biosynthetic process	1
tetrahydrofolate metabolic process	1

Indications & clinical

Indications

17 indications (1 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
neoplasm	4	MONDO:0005070	EFO:0000616
mesothelioma	3	MONDO:0005065	EFO:0000588
squamous cell carcinoma	3	MONDO:0005096	EFO:0000707
colorectal carcinoma	3	MONDO:0024331	EFO:1001951
colorectal adenocarcinoma	3	MONDO:0005008	EFO:0000365
colorectal neoplasm	3	MONDO:0005335	EFO:0004142
hepatocellular carcinoma	3	MONDO:0007256	EFO:0000182
rectal cancer	2	MONDO:0006519	EFO:1000657
esophageal squamous cell carcinoma	2	MONDO:0005580	EFO:0005922
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
bile duct adenoma	2	MONDO:0006108	EFO:1000123
nasopharyngeal carcinoma	2	MONDO:0015459	MONDO:0015459

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 40.

Phase distribution

Phase	Trials
PHASE2	23
PHASE3	6
PHASE1	6
PHASE4	3
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02557490	PHASE4	UNKNOWN	Oxaliplatin and Raltitrexed Treatment of Colorectal Cancer With Liver Metastases
NCT03196843	PHASE4	UNKNOWN	Radiotherapy Combine With Raltitrexed Versus Radiotherapy Alone in Older Patients With HNSCC.
NCT00002893	PHASE3	UNKNOWN	Palliative Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00004920	PHASE3	COMPLETED	Cisplatin With or Without Raltitrexed in Treating Patients With Malignant Mesothelioma of the Pleura
NCT00234429	PHASE2/PHASE3	COMPLETED	A Phase 2 Study of Tomudex & Iressa as Second Line Chemotherapy in Subjects With Colorectal Carcinoma
NCT02485548	PHASE3	UNKNOWN	Cisplatin Plus Raltitrexed or 5-fluorouracil Concurrent With Radiotherapy for Head and Neck Squamous Cell Cancer
NCT05231382	PHASE3	UNKNOWN	Hepatic Arterial Infusion of Raltetrexed With Oxaliplatin(SALOX) Versus FOLFOX in Advanced Hepatocellular Carcinoma
NCT05701436	PHASE3	UNKNOWN	Applicability of 3D-HDRA in Patients With Primary Liver Cancer: A Randomized Controlled Trial
NCT05766605	PHASE3	UNKNOWN	Applicability of PDOX in Patients With Primary Liver Cancer: A Randomized Controlled Trial
NCT05628038	PHASE2	RECRUITING	The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer
NCT06427005	PHASE2	RECRUITING	Fruquintinib Plus S-1 and Raltitrexed (RSF) for MCRC
NCT06652412	PHASE2	NOT_YET_RECRUITING	CGA Guided Ultrafractionated RT and Systemic Treatment in Elderly or Frail Patients with Inoperable Localized CRC
NCT00004254	PHASE2	COMPLETED	Raltitrexed in Treating Patients With Malignant Mesothelioma That Cannot Be Surgically Removed
NCT00590278	PHASE2	COMPLETED	A Phase-II Study Of TOMUDEX Plus Radiotherapy In Subject With Inoperable or Recurrent Rectal Cancer
NCT01348412	PHASE2	COMPLETED	Hepatic Arterial Chemotherapy With Raltitrexed and Oxaliplatin Versus Standard Chemotherapy in Unresectable Liver Metastases From Colorectal Cancer After Conventional Chemotherapy Failure
NCT01481545	PHASE2	COMPLETED	Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer
NCT01732380	PHASE2	UNKNOWN	A Phase-II Study Of Raltitrexed/Oxaliplatin Plus Radiotherapy Versus Radiotherapy In Subjects With Inoperable Esophageal Cancer
NCT02376452	PHASE2	UNKNOWN	Phase II Study of 2-weekly RAILIRI Versus FOLFIRI as Second-line Treatment in Advanced Colorectal Cancer Patients
NCT02618356	PHASE2	UNKNOWN	Combined Use of Raltitrexed and S-1 as Treatment for Patients With Metastasizing Colorectal Cancer
NCT02992886	PHASE2	COMPLETED	Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly
NCT03053167	PHASE2	UNKNOWN	Irinotecan Plus Raltitrexed as Second-line Treatment in Advanced Colorectal Cancer Patients
NCT03083613	PHASE2	COMPLETED	Raltitrexed and Paclitaxel for Gastric or Gastroesophageal Junction Adenocarcinoma
NCT03126071	PHASE2	UNKNOWN	Raltitrexed-based Chemotherapy Plus Bevacizumab in Retreated Patients With Advanced Colorectal Cancer
NCT03392103	PHASE2	UNKNOWN	Adjuvant IMRT With Concommitant Raltitrexed Chemotherapy for Locally Advanced Gastric Cancer After D0/D1 Radical Resection
NCT03585530	PHASE2	UNKNOWN	Raltitrexed Concurrent With Radiotherapy for Elderly Chinese Patients With Squamous Cell Carcinoma of Esophagus
NCT03813641	PHASE2	UNKNOWN	RALOX or CAPOX + Bevacizumab in the First-line Treatment of Advanced CRC(ROCB Study)
NCT03823079	PHASE2	UNKNOWN	Comparison of Interleukin-11 and rhTPO for Recurrent Colorectal Cancer Patients With Thrombocytopenia
NCT04241731	PHASE2	UNKNOWN	A Study of Cetuximab Plus Raltitrexed for Maintenance Treatment in Advanced Colorectal Cancer
NCT04581876	PHASE2	UNKNOWN	The Safety and Efficacy of the Combination of Raltitrexed for Injection and Nab-Paclitaxel in Advanced Pancreatic Cancer
NCT04582981	PHASE2	UNKNOWN	Fruquintinib and Raltitrexed Versus Fruquintinib Monotherapy in Advanced Colorectal Cancer
NCT05160896	PHASE2	UNKNOWN	SALIRI Based Regimen as First-line Treatment for Advanced Metastatic Colorectal Cancer
NCT05426811	PHASE1/PHASE2	UNKNOWN	Regorafenib Plus Raltitrexed as Third-line Treatment in Advanced Colorectal Cancer Patients
NCT05435313	PHASE2	UNKNOWN	Fruquintinib Combined With Tislelizumab and HAIC in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Therapy
NCT00001341	PHASE1	COMPLETED	A Phase I Trial of ZD1694 (TOMUDEX), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease
NCT00002828	PHASE1	COMPLETED	Chemotherapy With Raltitrexed and Fluorouracil in Treating Patients With Advanced Colorectal Cancer
NCT00002902	PHASE1	COMPLETED	Irinotecan Plus ICI D1694 in Treating Patients With Advanced Solid Tumors
NCT00003109	PHASE1	COMPLETED	Irinotecan Plus Raltitrexed in Treating Patients With Refractory Solid Tumors
NCT00003528	PHASE1	COMPLETED	Raltitrexed in Treating Children With Refractory Acute Leukemia
NCT04761185	PHASE1	COMPLETED	Raltitrexed in HIPEC

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

8 molecules share ≥1 primary target. Top 8 by shared-target count:

Molecule	Source	Status	Shared targets
FOLIC ACID	ChEMBL + PubChem	Phase 4 (approved)	TYMS
METHOTREXATE	ChEMBL + PubChem	Phase 4 (approved)	TYMS
PEMETREXED	ChEMBL + PubChem	Phase 4 (approved)	TYMS
PEMETREXED DISODIUM	ChEMBL + PubChem	Phase 4 (approved)	TYMS
PHENOLPHTHALEIN	ChEMBL	Phase 4 (approved)	TYMS
NOLATREXED	ChEMBL	Phase 3	TYMS
METESIND	ChEMBL	Phase 2	TYMS
OSI-7904	ChEMBL	Phase 2	TYMS