Tipiracil

Summary

Tipiracil (CHEMBL235668) is an approved small-molecule antineoplastic agent; indicated across 13 conditions including colorectal neoplasm and cholangiocarcinoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Indications: 13 conditions
• Clinical trials: 67
• Chemistry: 242.66 Da · C9H11ClN4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL235668
Name	Tipiracil
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	6323266
ChEBI	CHEBI:90879
Molecular formula	C9H11ClN4O2
Molecular weight	242.66
InChIKey	QQHMKNYGKVVGCZ-UHFFFAOYSA-N

SMILES: C1CC(=N)N(C1)CC2=C(C(=O)NC(=O)N2)Cl

IUPAC name: 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione

ChEBI definition: A member of the class of pyrimidones that is uracil substituted by chloro and (2-iminopyrrolidin-1-yl)methyl groups at positions 5 and 6 respectively. Used (as the hydrochloride salt) in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer.

Pharmacological roles (ChEBI): antineoplastic agent, EC 2.4.2.4 (thymidine phosphorylase) inhibitor.

Also known as: MA-1, Tipiracil, Tipiracilo, TPI (freebase), TIPIRACIL, Tipiracil (hydrochloride), tipiracil

Parent form; salt/anhydrous children: CHEMBL65375

Patent coverage: 1,301 distinct patent families (2,948 SureChEMBL compound mentions), from 1 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
	CoV Non-structural protein 15	Inhibition

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Thymidine phosphorylase, Thymidine phosphorylase.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TYMP	8.89	Ki	1.3	nM	CHEMBL_ACT_2002378
TYMP	8.68	Ki	2.1	nM	CHEMBL_ACT_2002404
TYMP	8.3	Ki	5	nM	CHEMBL_ACT_312875
TYMP	7.77	Ki	17	nM	CHEMBL_ACT_944461
TYMP	7.7	Ki	20	nM	CHEMBL_ACT_19364712
TYMP	7.7	IC50	20	nM	CHEMBL_ACT_944460
TYMP	7.46	IC50	35	nM	CHEMBL_ACT_19364711
TYMP	7.46	IC50	35	nM	CHEMBL_ACT_312876
P07650	7.46	Ki	35	nM	CHEMBL_ACT_3197548

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

13 indications (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
colorectal neoplasm	3	MONDO:0005335	EFO:0004142
cholangiocarcinoma	2	MONDO:0019087	EFO:0005221
breast neoplasm	2	MONDO:0021100	MONDO:0007254
rectal cancer	2	MONDO:0006519	EFO:1000657
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
gastric adenocarcinoma	2	MONDO:0005036	EFO:0000503
malignant pancreatic neoplasm	2	MONDO:0009831	EFO:1000359
colon carcinoma	2	MONDO:0002032	EFO:1001950
neoplasm	1	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	1	MONDO:0005233	EFO:0003060

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

Clinical trials

Total trials: 67.

Phase distribution

Phase	Trials
PHASE2	29
PHASE3	11
PHASE1/PHASE2	10
PHASE1	8
Not specified	8
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03869892	PHASE3	ACTIVE_NOT_RECRUITING	Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy.
NCT06343116	PHASE3	NOT_YET_RECRUITING	Nimotuzumab Combined With Trifluridine/Tipiracil in the Treatment of Refractory Metastatic Colorectal Cancer
NCT07270991	PHASE3	RECRUITING	Trifluridine/Tipiracil + Fruquintinib Versus Trifluridine/Tipiracil Alone for Metastatic Oeso-gastric Adenocarcinoma
NCT07361003	PHASE3	RECRUITING	A Phase Ib/III Study of Suvemcitug Plus FTD/TPI in Participants With Refractory Metastatic Colorectal Cancer
NCT07483684	PHASE3	NOT_YET_RECRUITING	A Clinical Study to Evaluate Injection TQB2102 for the Treatment of Patients With HER2 IHC3+ Advanced Colorectal Cancer Who Progressed After Treatment With Oxaliplatin, Irinotecan and Fluoropyrimidine-Based Drugs
NCT07525206	PHASE3	NOT_YET_RECRUITING	A Study to Access Intravenous (IV) Telisotuzumab Adizutecan in Combination With IV Bevacizumab Compared to Standard of Care IV Bevacizumabin Combination With Oral Trifluridine and Tipiracil in Adult Participants With Refractory Metastatic Colorectal Cancer
NCT03306394	PHASE3	COMPLETED	A Study of Trifluridine/Tipiracil (Also Known as S 95005 or TAS-102) in Patients With a Pretreated Colorectal Cancer That Has Spread (Metastatic).
NCT04457297	PHASE3	COMPLETED	Initial Attack on Latent Metastasis Using TAS-102 for ct DNA Identified Colorectal Cancer Patients After Curative Resection
NCT04737187	PHASE3	COMPLETED	Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients
NCT05198934	PHASE3	COMPLETED	Sotorasib and Panitumumab Versus Investigator’s Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
NCT05223673	PHASE3	TERMINATED	Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer
NCT04166604	PHASE2	ACTIVE_NOT_RECRUITING	LONsurf and G-CSF Use: Being On A Right Dose-intensity to Optimize Treatment Efficacy
NCT04564898	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients.
NCT05083481	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of ASP1570 Taken by Itself, or ASP1570 Taken Together With Either Pembrolizumab, Standard Therapies, or Both, in Adults With Solid Tumors
NCT05476796	PHASE2	RECRUITING	Oxaliplatin ± Nivolumab in Combination With Trifluridine/Tipiracil or 5-fluorouracile in Frail Patients With Advanced, Recurrent or Metastatic Gastric, Oesophageal or Gastroesophageal Junction Cancer
NCT05919264	PHASE1/PHASE2	RECRUITING	FOG-001 in Locally Advanced or Metastatic Solid Tumors
NCT05927857	PHASE1/PHASE2	RECRUITING	Ramucirumab (Cyramza), Nal-IRI (ONIVYDE) and Trifluridine/Tipiracil (Lonsurf) in Second Line Metastatic Gastric Cancer .
NCT05965531	PHASE2	RECRUITING	Treating Locally Advanced Rectal Cancer With TAS-102 Chemotherapy Plus Neoadjuvant Radiotherapy
NCT05970705	PHASE2	RECRUITING	Regorafenib Combined With TAS-102 Versus Regorafenib Monotherapy in Third or Later Line Therapy of mCRC
NCT06202001	PHASE1/PHASE2	RECRUITING	Irinotecan, TAS-102 Plus Bevacizumab as a Second-Line Therapy in mCRC Patients
NCT06242067	PHASE2	RECRUITING	Second-line Treatment of Metastatic Colorectal Cancer
NCT06403709	PHASE2	ACTIVE_NOT_RECRUITING	Irinotecan, TAS-102 Plus Bevacizumab as a Third-Line or Beyond Therapy in mCRC Patients
NCT06485713	PHASE2	RECRUITING	Efficacy and Safety of Trifluridine/Tipiracil Combined With Fufuquitinib for Third-line Treatment of mCRC
NCT06680622	PHASE2	ACTIVE_NOT_RECRUITING	Bemarituzumab in FGFR2b+ Patients With Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed at Least One Prior Line of Palliative Chemotherapy
NCT06711471	PHASE2	RECRUITING	Trifluridine/tipiracil (TAS-102), Bevacizumab, and Camrelizumab As Third-line or Later-line Therapy of Gastric Cancer
NCT06856837	PHASE2	RECRUITING	- IKF/AIO-QUINTIS - Evaluating Fruquintinib in Combination With Tislelizumab in Microsatellite Stable / Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Cancer Without Active Liver Metastases
NCT07012954	PHASE1/PHASE2	RECRUITING	ctDNA-Guided Cetuximab or Bevacizumab Plus Trifluridine/Tipiracil in RAS/BRAF Wild-Type mCRC
NCT07071844	PHASE2	NOT_YET_RECRUITING	BETWEEN: Biweekly Bevacizumab + Trifluridine/Tipiracil to Reduce Grade 3-4 Neutropenia in mCRC Patients
NCT07085169	PHASE2	RECRUITING	Low-dose Trifluridine/Tipiracil With Bevacizumab in mCRC
NCT07146646	PHASE2	RECRUITING	Trifluridine/Tipiracil + Oxaliplatin in Participants With Advanced or Metastatic Biliary Tract Cancer
NCT07280377	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab
NCT07286695	PHASE2	NOT_YET_RECRUITING	Fruquintinib Combined With Trifluridine/Tipiracil Versus Bevacizumab Combined With Trifluridine/Tipiracil for Advanced Metastatic Colorectal Cancer
NCT07381764	PHASE2	NOT_YET_RECRUITING	ROMANCE: Irinotecan Plus Cetuximab Rechallenge Versus Trifluridine/Tipiracil Plus Bevacizumab in Molecularly Selected Metastatic Colorectal Cancer
NCT07491159	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fruquintinib Plus Checkpoint Inhibitor Combined or Sequential TAS-102 in Colorectal Cancer Patients Who Progressed on Second-line Standard Therapy: a Prospective, Multi-cohort, Single-centered, Phase Ib/II Study
NCT07535632	PHASE2	NOT_YET_RECRUITING	SBRT Followed by PD-1 Inhibitor, Bevacizumab and TAS-102 as Third-Line Therapy for Recurrent/Metastatic Colorectal Cancer
NCT03278106	PHASE2	COMPLETED	TAS-102 in Treating Advanced Biliary Tract Cancers
NCT03799731	PHASE2	COMPLETED	Study for Evaluation of Murlentamab (GM102) Anti-tumoral Activity in Colorectal Cancers
NCT04076761	PHASE2	TERMINATED	Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma
NCT04149444	PHASE2	WITHDRAWN	A Study of Trifluridine/Tipiracil in Triple Negative Metastatic Breast Cancer
NCT04393298	PHASE1/PHASE2	COMPLETED	A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors

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

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).