Irinotecan

Summary

Irinotecan (CHEMBL481) is an approved small-molecule EC 5.99.1.2 (DNA topoisomerase) inhibitor (ATC L01CE02) targeting TOP1; indicated across 88 conditions including neoplasm and ewing sarcoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01CE02
• Targets: 1 (TOP1)
• Indications: 88 conditions
• Clinical trials: 847
• Chemistry: 586.7 Da · C33H38N4O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL481
Name	Irinotecan
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	60838
ChEBI	CHEBI:80630
ATC	L01CE02
Molecular formula	C33H38N4O6
Molecular weight	586.7
InChIKey	UWKQSNNFCGGAFS-XIFFEERXSA-N

SMILES: CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)[C@@]4(CC)O)C2=NC5=C1C=C(C=C5)OC(=O)N6CCC(CC6)N7CCCCC7

IUPAC name: [(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate

ChEBI definition: A member of the class of pyranoindolizinoquinolines that is the carbamate ester obtained by formal condensation of the carboxy group of [1,4’-bipiperidine]-1’-carboxylic acid with the phenolic hydroxy group of (4S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3’,4’:6,7]indolizino[1,2- hydrochloride]quinoline-3,14-dione. Used (in the form of its hydrochloride salt trihydrate) in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. It is converted via hydrolysis of the carbamate linkage to its active metabolite, SN-38, which is ~1000 times more active.

Pharmacological roles (ChEBI): apoptosis inducer, EC 5.99.1.2 (DNA topoisomerase) inhibitor, antineoplastic agent, prodrug.

Also known as: Biotecan, Irinophore c, Irinotecan, NSC-728073, irinotecan, Irinotecan (CPT-11), SID124893595, Camptosar, Camptothecin (CPT-11,lactone form), IRINOTECAN, IRT, IRINOTECAN HYDROCHLORIDE HYDRATE

Parent form; salt/anhydrous children: CHEMBL541887, CHEMBL1200512, CHEMBL3989514

Patent coverage: 41,662 distinct patent families (159,900 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 159,175 (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
TOP1	DNA topoisomerase I	Inhibition		93% (common-essential)	P11387

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Solute carrier family 22 member 2, Multidrug and toxin extrusion protein 1, Multidrug and toxin extrusion protein 2, Muscarinic acetylcholine receptor M4, Alpha-2C adrenergic receptor, Solute carrier family 22 member 3, Acetylcholinesterase, Interstitial collagenase, Cytochrome P450 3A4, Acetylcholinesterase.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 17 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P04058	7.58	Ki	26.4	nM	CHEMBL_ACT_2341258
ACHE	7.3	Ki	50.5	nM	CHEMBL_ACT_2341257
CHRM4	6.66	Ki	217	nM	CHEMBL_ACT_7761171
ADRA2C	6.34	Ki	461	nM	CHEMBL_ACT_7759024
CHRM4	5.81	IC50	1556	nM	CHEMBL_ACT_7761170
ACHE	5.74	IC50	1827	nM	CHEMBL_ACT_7759003
SLC47A1	5.68	IC50	2100	nM	CHEMBL_ACT_12636137
SLC22A2	5.57	IC50	2700	nM	CHEMBL_ACT_12636189
ADRA2C	5.5	IC50	3171	nM	CHEMBL_ACT_7759023
SLC47A1	5.37	IC50	4300	nM	CHEMBL_ACT_12636128
MMP1	5.22	IC50	6060	nM	CHEMBL_ACT_7763207
SLC47A2	5.1	IC50	7900	nM	CHEMBL_ACT_12636148
SLC47A1	5.1	IC50	7900	nM	CHEMBL_ACT_12637850

Target pathways

Aggregated over 1 target gene(s): TOP1.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
SUMOylation of DNA replication proteins	1	TOP1

Dominant GO biological processes

GO term	Targets
DNA replication	1
DNA topological change	1
chromatin remodeling	1
chromosome segregation	1
circadian rhythm	1
response to temperature stimulus	1
rRNA transcription	1
response to xenobiotic stimulus	1
response to gamma radiation	1
programmed cell death	1
animal organ regeneration	1
circadian regulation of gene expression	1
embryonic cleavage	1
response to cAMP	1
cellular response to luteinizing hormone stimulus	1

Indications & clinical

Indications

88 indications (2 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
Ewing sarcoma	3	MONDO:0012817	EFO:0000174
gastric carcinoma	3	MONDO:0004950	EFO:0000178
hepatocellular carcinoma	3	MONDO:0007256	EFO:0000182
colorectal adenocarcinoma	3	MONDO:0005008	EFO:0000365
gastric adenocarcinoma	3	MONDO:0005036	EFO:0000503
neuroblastoma	3	MONDO:0005072	EFO:0000621
small cell lung carcinoma	3	MONDO:0008433	EFO:0000702
cervical carcinoma	3	MONDO:0005131	EFO:0001061
cervical adenocarcinoma	3	MONDO:0005153	EFO:0001416
exocrine pancreatic carcinoma	3	MONDO:0005192	EFO:0002618
carcinoma of esophagus	3	MONDO:0019086	EFO:0002916
brain neoplasm	3	MONDO:0021211	EFO:0003833
pancreatic neoplasm	3	MONDO:0021040	EFO:0003860
breast neoplasm	3	MONDO:0021100	EFO:0003869
gastric neoplasm	3	MONDO:0021085	EFO:0003897
colorectal neoplasm	3	MONDO:0005335	EFO:0004142
colonic neoplasm	3	MONDO:0005401	EFO:0004288
cholangiocarcinoma	3	MONDO:0019087	EFO:0005221
esophageal squamous cell carcinoma	3	MONDO:0005580	EFO:0005922
rectal cancer	3	MONDO:0006519	EFO:1000657
colorectal carcinoma	3	MONDO:0024331	EFO:1001951
ganglioneuroblastoma	3	MONDO:0005035	EFO:0000502
hepatoblastoma	3	MONDO:0018666	EFO:1000292
intrahepatic cholangiocarcinoma	3	MONDO:0003210	EFO:1001961
brain cancer	3	MONDO:0001657	MONDO:0001657
neuroendocrine carcinoma	3	MONDO:0002120	MONDO:0002120
rectal neoplasm	3	MONDO:0002165	MONDO:0002165
lung neoplasm	3	MONDO:0021117	MONDO:0008903
colon carcinoma	3	MONDO:0002032	EFO:1001950
pancreatic ductal adenocarcinoma	3	MONDO:0005184	MONDO:0005184
carcinoma	2	MONDO:0004993	EFO:0000313
central nervous system cancer	2	MONDO:0002714	EFO:0000326
glioblastoma	2	MONDO:0018177	EFO:0000519
leukemia	2	MONDO:0005059	EFO:0000565
lymphoma	2	MONDO:0005062	EFO:0000574
sarcoma	2	MONDO:0005089	EFO:0000691
squamous cell carcinoma	2	MONDO:0005096	EFO:0000707
anaplastic astrocytoma	2	MONDO:0016684	EFO:0002499
rhabdomyosarcoma	2	MONDO:0005212	EFO:0002918
medulloblastoma	2	MONDO:0007959	EFO:0002939
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
biliary tract neoplasm	2	MONDO:0005304	EFO:0003891
non-Hodgkin lymphoma	2	MONDO:0018908	EFO:0005952
pineoblastoma	2	MONDO:0016722	EFO:1000475
gliosarcoma	2	MONDO:0016681	EFO:1001465
ovarian carcinoma	2	MONDO:0005140	EFO:0001075
ovarian neoplasm	2	MONDO:0021068	EFO:0003893
head and neck cancer	2	MONDO:0005627	EFO:0006859
angiosarcoma	2	MONDO:0016982	EFO:0003968
pancreatic endocrine carcinoma	2	MONDO:0005893	EFO:0007416
central nervous system neoplasm	2	MONDO:0006130	EFO:1000158
peritoneal neoplasm	2	MONDO:0006901	MONDO:0002087
fallopian tube neoplasm	2	MONDO:0021092	MONDO:0002158
kidney cancer	2	MONDO:0002367	MONDO:0002367
ovarian cancer	2	MONDO:0008170	MONDO:0008170
Wilms tumor	2	MONDO:0006058	MONDO:0019004
glioma	2	MONDO:0021042	MONDO:0100342
bone cancer	2	MONDO:0002129	EFO:1000350
astrocytoma (excluding glioblastoma)	2	MONDO:0019781	EFO:0000272
bone neoplasm	2	MONDO:0019060	EFO:0003820
bile duct carcinoma	2	MONDO:0005496	EFO:0005540
paraganglioma	2	MONDO:0000448	EFO:1000453
adenocarcinoma	2	MONDO:0004970	MONDO:0003219
gallbladder neoplasm	2	MONDO:0021253	MONDO:0005411
anaplastic oligodendroglioma	1	MONDO:0016696	EFO:0002501
mesothelioma	1	MONDO:0005065	EFO:0000588
diffuse intrinsic pontine glioma	1	MONDO:0006033	EFO:1000026
endometrial carcinoma	1	MONDO:0002447	EFO:1001512
carcinoid tumor	1	MONDO:0005369	MONDO:0024503
colon adenocarcinoma	1	MONDO:0002271	EFO:1001949
hereditary breast ovarian cancer syndrome	1	MONDO:0003582	Orphanet:145
desmoplastic small round cell tumor	0	MONDO:0019373	EFO:1000895

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

Clinical trials

Total trials: 847.

Phase distribution

Phase	Trials
PHASE2	428
PHASE1	145
PHASE3	115
PHASE1/PHASE2	103
Not specified	27
PHASE4	11
PHASE2/PHASE3	11
EARLY_PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06467786	PHASE4	RECRUITING	Study on the Therapeutic Effect of Irinotecan Liposomes in Small Cell Lung Cancer
NCT06499610	PHASE4	NOT_YET_RECRUITING	Clinical Study of Irinotecan Liposome Combination Therapy for Advanced Gastric Cancer
NCT06951841	PHASE4	NOT_YET_RECRUITING	Prospective, Single-arm, Phase II Clinical Study of Irinotecan Hydrochloride Liposome Injection Combined With Platinum and Immune Checkpoint Inhibitors Combined With Anlotinib for the Maintenance of Extensive Small Cell Lung Cancer After First-line Induction
NCT07014540	PHASE4	NOT_YET_RECRUITING	A Irinotecan Liposome Trial of in Advanced Neuroendocrine Carcinoma
NCT07094893	PHASE4	NOT_YET_RECRUITING	Anti-EGFR Agents in Patients With Right-sided Advanced Colorectal Cancer With Wild-type RAS and AREG/EREG High Status
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00220168	PHASE4	COMPLETED	Phase II Trial Evaluating Irinotecan and Capecitabine Relapsed/Refractory Upper GI Tumours
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01588990	PHASE4	COMPLETED	A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
NCT02348450	PHASE4	UNKNOWN	Irinotecan Plus Cisplatin Compared With Etoposide Plus Cisplatin for Extensive Stage Small-cell Lung Cancer
NCT02582970	PHASE4	COMPLETED	A Study of Bevacizumab (Avastin) in Combination With Chemotherapy in Participants With Metastatic Cancer of the Colon or Rectum
NCT02885753	PHASE3	RECRUITING	Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver
NCT02919787	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Nordic Pancreatic Cancer Trial (NorPACT) - 1
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT03829462	PHASE3	ACTIVE_NOT_RECRUITING	Assessing a Regorafenib-irinotecan Combination Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients
NCT04008030	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator’s Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)
NCT04094688	PHASE3	ACTIVE_NOT_RECRUITING	Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer
NCT04221035	PHASE3	RECRUITING	High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)
NCT04342910	PHASE3	RECRUITING	Study to Evaluate the Efficacy and Safety of Camrelizumab and Apatinib in Patients With GC/GEJC
NCT04415853	PHASE3	RECRUITING	Study of Larotinib in Unresectable Advanced or Recurrent Esophageal Cancer
NCT04607421	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
NCT04776655	PHASE3	RECRUITING	Study in mCRC Patients RAS/BRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB
NCT04861558	PHASE3	RECRUITING	Efficacy of Hyperthermic Intraperitoneal Chemotherapy
NCT04879368	PHASE3	ACTIVE_NOT_RECRUITING	RegoNivo vs Standard of Care Chemotherapy in AGOC
NCT05239741	PHASE3	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Chinese Participants With Stage IV Colorectal Cancer (MK-3475-C66)
NCT05314998	PHASE3	NOT_YET_RECRUITING	Adjuvant Trial in Patients With Resected PDAC Randomized to Allocation of Oxaliplatin- or Gemcitabine-based Chemotherapy by Standard Clinical Criteria or by a Transcriptomic Treatment Specific Stratification Signature
NCT05427383	PHASE2/PHASE3	RECRUITING	KN026 in Combination With Chemotherapy in HER2 Positive Gastric Cancer Subjects Who Have Failed First-line Therapy
NCT05677490	PHASE3	RECRUITING	mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
NCT05863195	PHASE3	RECRUITING	Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial
NCT06123494	PHASE3	RECRUITING	SHR-A1811 for Subjects With Her2-positive Gastric Cancer and Gastroesophageal Junction Adenocarcinoma After Progression on or After First-line Anti-HER2 Therapy-containing Regimen
NCT06128837	PHASE3	RECRUITING	Study of LY01610 in Patients With Recurrent Small Cell Lung Cancer
NCT06172296	PHASE3	RECRUITING	Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
NCT06194734	PHASE3	RECRUITING	A Study of KC1036 Versus Investigator’s Choice of Chemotherapy in Patients With Advanced Esophageal Cancer
NCT06250972	PHASE3	RECRUITING	Radiotherapy to Patients With CA19-9-elevated Advanced Pancreatic Cancer
NCT06304974	PHASE3	ACTIVE_NOT_RECRUITING	A Study Comparing BL-B01D1 With Chemotherapy of Physician’s Choice in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma(PANKU-Esophagus01)
NCT06346392	PHASE3	ACTIVE_NOT_RECRUITING	AZD0901 Compared With Investigator’s Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2
NCT06351020	PHASE3	ACTIVE_NOT_RECRUITING	LM-302 for the Treatment of Subjects With Claudin18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma.
NCT06356311	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) in Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-2870-015)
NCT06401330	PHASE3	RECRUITING	A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (3) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for irinotecan and UGT1A1	DPWG	UGT1A1	yes	yes
Annotation of RNPGx Guideline for irinotecan and UGT1A1	RNPGx	UGT1A1	yes	yes
Annotation of AIOM Guideline for irinotecan and UGT1A1	AIOM	UGT1A1	yes	yes

PharmGKB also curates 54 clinical and 435 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

12 molecules share ≥1 primary target. Top 12 by shared-target count:

Molecule	Source	Status	Shared targets
AMSACRINE	ChEMBL	Phase 4 (approved)	TOP1
DOXORUBICIN	ChEMBL	Phase 4 (approved)	TOP1
RIBAVIRIN	ChEMBL	Phase 4 (approved)	TOP1
TOPOTECAN	ChEMBL	Phase 4 (approved)	TOP1
EDOTECARIN	ChEMBL	Phase 3	TOP1
HYDROXYCAMPTOTHECIN	ChEMBL	Phase 3	TOP1
YOHIMBINE	ChEMBL	Phase 3	TOP1
7-ETHYL-10-HYDROXYCAMPTOTHECIN	ChEMBL	Phase 2	TOP1
9-AMINOCAMPTOTHECIN	ChEMBL	Phase 2	TOP1
OLEIC ACID	ChEMBL	Phase 2	TOP1
STALLIMYCIN	ChEMBL	Phase 2	TOP1
podofilox	PubChem	Approved	TOP1