IRINOTECAN HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H38N4O6.ClH.3H2O
Molecular Weight	677.186
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCc1c2cc(ccc2nc-3c1Cn4c3cc5c(COC(=O)[C@@]5(CC)O)c4=O)OC(=O)N6CCC(CC6)N7CCCCC7.Cl.O.O.O

InChI

InChIKey=KLEAIHJJLUAXIQ-JDRGBKBRSA-N

InChI=1S/C33H38N4O6.ClH.3H2O/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2;;;;/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3;1H;3*1H2/t33-;;;;/m0..../s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.4609
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C33H38N4O6
Molecular Weight	586.6793
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf | https://www.drugs.com/cdi/irinotecan.html | https://www.ncbi.nlm.nih.gov/pubmed/14988754

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is sold under the brand name Camptosar among others. CAMPTOSAR is a topoisomerase inhibitor indicated for: • First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. • Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase I 54 Target ID: CHEMBL1781 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9655905 \| https://www.ncbi.nlm.nih.gov/pubmed/8182764 \| https://www.ncbi.nlm.nih.gov/pubmed/8388965 \| https://www.ncbi.nlm.nih.gov/pubmed/14988754	Inhibitor 7728

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic carcinoma of the colon or rectum 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf	Primary		Approved 8043	CAMPTOSAR Approved Use CAMPTOSAR is a topoisomerase inhibitor indicated for: • First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. (1) • Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. Launch Date 8.3471041E11

C_max

Value	Dose	Co-administered	Analyte	Population
3392 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	340 mg/m² single, intravenous dose: 340 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1660 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
20604 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	340 mg/m² single, intravenous dose: 340 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
10200 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	340 mg/m² single, intravenous dose: 340 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
51% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020571s051lbl.pdf	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		IRINOTECAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
21 mg/m2 1 times / day multiple, oral MTD Dose: 21 mg/m2, 1 times / day Route: oral Route: multiple Dose: 21 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30406838/	unhealthy, adult n = 12 Health Status: unhealthy Condition: solid tumors Age Group: adult Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/30406838/	Other AEs: Fatigue, Weight loss... Other AEs: Fatigue (grade 1-2, 33.3%) Weight loss (grade 1-2, 33.3%) Diarrhea (grade 1-2, 50%) Nausea (grade 1-2, 58.3%) Vomiting (grade 1-2, 50%) Cholinergic syndrome (grade 1-2, 33.3%) Mucositis (grade 1-2, 33.3%) Dyspnea (grade 1-2, 8.3%) Fever (grade 1-2, 8.3%) Fatigue (grade 3, 8.3%) Diarrhea (grade 3, 8.3%) Nausea (grade 3, 8.3%) Vomiting (grade 3, 8.3%) Cholinergic syndrome (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/30406838/
290 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 290 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 290 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10873073/	unhealthy, adult n = 7 Health Status: unhealthy Condition: solid tumors Age Group: adult Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/10873073/	Other AEs: Leukopenia, Leukopenia... Other AEs: Leukopenia (grade 2, 1 patient) Leukopenia (grade 3, 2 patients) Leukopenia (grade 4, 1 patient) Neutropenia (grade 2, 2 patients) Neutropenia (grade 3, 2 patients) Neutropenia (grade 4, 1 patient) Nausea (grade 1, 4 patients) Nausea (grade 3, 1 patient) Vomiting (grade 4, 1 patient) Diarrhea (grade 1, 2 patients) Diarrhea (grade 2, 3 patients) Diarrhea (grade 4, 1 patient) Anorexia (grade 1, 3 patients) Anorexia (grade 2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10873073/
320 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 320 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 320 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10873073/	unhealthy, adult n = 8 Health Status: unhealthy Condition: solid tumors Age Group: adult Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/10873073/	Other AEs: Leukopenia, Leukopenia... Other AEs: Leukopenia (grade 1, 4 patients) Leukopenia (grade 2, 1 patient) Leukopenia (grade 3, 2 patients) Neutropenia (grade 1, 2 patients) Neutropenia (grade 2, 2 patients) Neutropenia (grade 4, 2 patients) Thrombocytopenia (grade 1, 2 patients) Nausea (grade 1, 3 patients) Nausea (grade 2, 3 patients) Nausea (grade 3, 2 patients) Vomiting (grade 1, 2 patients) Vomiting (grade 2, 2 patients) Vomiting (grade 3, 1 patient) Vomiting (grade 4, 1 patient) Diarrhea (grade 1, 3 patients) Diarrhea (grade 2, 2 patients) Diarrhea (grade 3, 1 patient) Diarrhea (grade 4, 1 patient) Anorexia (grade 1, 3 patients) Anorexia (grade 2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10873073/

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:80630	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:80630
ChemicalBook	CB1124156	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1124156
MolPort	MolPort-003-848-231	https://www.molport.com/shop/molecule-link/MolPort-003-848-231
Selleck Chemicals	Irinotecan	http://www.selleckchem.com/products/Irinotecan.html
ZINC	ZINC000001612996	http://zinc15.docking.org/substances/ZINC000001612996
eMolecules	31588824	https://www.emolecules.com/cgi-bin/more?vid=31588824
eMolecules	901988	https://www.emolecules.com/cgi-bin/more?vid=901988

PubMed

Title	Date	PubMed

Characterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2.	2000 Mar 1	10728672
A dose-finding study of irinotecan (CPT-11) plus a four-day continuous 5-fluorouracil infusion in advanced colorectal cancer.	2001	11340371
Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients. A phase I/II study of the Southern Italy Cooperative Oncology Group.	2001	11244327
Lung cancer: therapeutic options for stage IV and recurrent NSCLC.	2001	11224988
Chemoradiation in locally advanced non-small cell lung cancer.	2001	11224987
Irinotecan plus fluorouracil/leucovorin for metastatic colorectal cancer: a new survival standard.	2001	11161231
Irinotecan: a new agent comes of age.	2001	11161229
Gemcitabine: progress in the treatment of pancreatic cancer.	2001	11150902
[Irinotecan (CPT-11) therapy for advanced gastric cancer].	2001 Apr	11424411
Safe administration of irinotecan, oxaliplatin and raltitrexed in a DPD-deficient patient with metastatic colon cancer.	2001 Apr	11398894
A phase II trial of irinotecan (CPT-11) for unresectable biliary tree carcinoma.	2001 Apr	11398883
Use of a modified ornithine decarboxylase promoter to achieve efficient c-MYC- or N-MYC-regulated protein expression.	2001 Apr 1	11306486
Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues.	2001 Apr 15	11309308
Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients.	2001 Apr 15	11291056
Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines.	2001 Feb	11207057
Combination chemotherapy in patients with malignant pleural effusions from non-small cell lung cancer : cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support.	2001 Feb	11171707
New state of the art in small-cell lung cancer.	2001 Jan	11221023
Irinotecan in combined-modality therapy for locally advanced non-small-cell lung cancer.	2001 Jan	11221019
Rationale and dose-finding studies of the combination of irinotecan and a taxane on a weekly schedule.	2001 Jan	11221018
Treatment of non-small-cell lung cancer in North America: the emerging role of irinotecan.	2001 Jan	11221017
Establishment of the standard regimen for non-small-cell lung cancer in Japan.	2001 Jan	11221016
Irinotecan in small-cell lung cancer: the US experience.	2001 Jan	11221015
Oral fluoropyrimidine-based combination therapy in gastrointestinal cancer.	2001 Jan	11219983
Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells.	2001 Jan	11205902
[A case of small cell carcinoma of esophagus successfully treated by chemotherapy with CPT-11 and CDDP].	2001 Jan	11201121
Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan.	2001 Jan	11156563
A phase II study of irinotecan in patients with advanced hepatocellular carcinoma.	2001 Jan 1	11148565
Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor.	2001 Jan 15	11212269
Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer.	2001 Jan 25	11191663
The changing face of chemotherapy in colorectal cancer.	2001 Jan 5	11139304
[Refinement and role of the diagnosis of Gilbert disease with molecular biology].	2001 Jan-Feb	11174102
New chemotherapy approaches in colorectal cancer.	2001 Jul	11429486
Control of irinotecan-induced diarrhea by octreotide after loperamide failure.	2001 Jun	11430421
Hepatic extraction, metabolism, and biliary excretion of irinotecan in the isolated perfused rat liver.	2001 Jun	11357175
Irinotecan plus cisplatin in advanced gastric or gastroesophageal junction carcinoma.	2001 Mar	11301842
Determinants of prognosis and response to therapy in colorectal cancer.	2001 Mar	11177741
Roles of NF-kappaB and 26 S proteasome in apoptotic cell death induced by topoisomerase I and II poisons in human nonsmall cell lung carcinoma.	2001 Mar 16	11115510
Preliminary study of fortnightly irinotecan hydrochloride plus cisplatin therapy in patients with advanced gastric and colorectal cancer.	2001 May	11391851
[A modified administrated schedule for combination therapy with irinotecan and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical cancer--a report of 2 cases as a pilot study].	2001 May	11383222
[Platinum compounds in cancer therapy--past, present, and future].	2001 May	11383210
CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver.	2001 May	11376565
Impact on survival following successful neoadjuvant chemotherapy and radical surgery for Stage IIb bulky and Stage IIIb cervical cancer.	2001 May	11330973
Integrating the oral fluoropyrimidines into the management of advanced colorectal cancer.	2001 May	11313169
Potentiation of antitumor activity of irinotecan by chemically modified oligonucleotides.	2001 May	11295057
Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition.	2001 May 1	11325813
Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer.	2001 May 15	11352961

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Colorectal Cancer Either as a single agent or in combination with fluorouracil and leucovorin: 125 mg/m2 intravenously over 90 minutes once a week for four doses or as a single agent: 350 mg/m2 intravenously over 90 minutes every three weeks or in combination with fluorouracil and leucovorin: 180 mg/m2 intravenously over 90 minutes every other week for three doses.

Route of Administration: Intravenous

In Vitro Use Guide

The sensitivity to CPT-11 (Irinotecan) alone, of 5 human colon-cancer cell lines, expressed as IC50 values, varied between 2.5 and 6.1uM. The anti-proliferative effectsof the active metabolite SN-38 showed IC50 values between 5.6 and 38 nM, 130 to 570 times lower than those measured for CPT-11 alone. The sensitivity to SN-38 was highest in LS174T and COLO320 cells, intermediate in SW1398 cells and lowest in COLO 205 and WiDr cells.

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:02:56 UTC 2021` Edited by `admin` on `Fri Jun 25 21:02:56 UTC 2021`
Record UNII	042LAQ1IIS
Record Status	`Validated (UNII)`
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Name

Type

Language

IRINOTECAN HYDROCHLORIDE

Official Name

English

IRINOTECAN HYDROCHLORIDE [MART.]

Common Name

English

ONIVYDE

Brand Name

English

U-101,440E

Code

English

IRINOTECAN HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

IRINOTECAN HYDROCHLORIDE TRIHYDRATE [EP MONOGRAPH]

Common Name

English

IRINOTECAN HYDROCHLORIDE [USP-RS]

Common Name

English

IRINOTECAN HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

IRINOTECAN HYDROCHLORIDE HYDRATE

Common Name

English

NSC-759878

Code

English

XELIRI COMPONENT IRINOTECAN HYDROCHLORIDE

Common Name

English

IRINOTECAN HYDROCHLORIDE [USAN]

Common Name

English

(1,4'-BIPIPERIDINE)-1'-CARBOXYLIC ACID, 4,11-DIETHYL-3,4,12,14-TETRAHYDRO-4-HYDROXY-3,14-DIOXO-1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLIN-9-YL ESTER, MONOHYDROCHLORIDE, TRIHYDRATE, (S)-

Common Name

English

CPT-11

Code

English

CAMPTO

Brand Name

English

IRINOTECAN HYDROCHLORIDE TRIHYDRATE

Common Name

English

IRINOTECAN MONOHYDROCHLORIDE TRIHYDRATE [WHO-DD]

Common Name

English

(+)-7-ETHYL-10-HYDROXYCAMPTOTHECINE 10-(1,4'-BIPIPERIDINE)-1'-CARBOXYLATE, MONOHYDROCHLORIDE, TRIHYDRATE

Common Name

English

IRINOTECAN HYDROCHLORIDE TRIHYDRATE [EMA EPAR]

Common Name

English

DQ-2805

Code

English

IRINOTECAN HYDROCHLORIDE TRIHYDRATE [MI]

Common Name

English

IRINOTECAN HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

CAMPTOSAR

Brand Name

English

IRINOTECAN HYDROCHLORIDE [VANDF]

Common Name

English

IRINOTECAN MONOHYDROCHLORIDE TRIHYDRATE

Common Name

English

U-101440E

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/11/933