IRINOTECAN HYDROCHLORIDE ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H38N4O6.ClH
Molecular Weight	623.139
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of IRINOTECAN HYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

Cl.CCC1=C2C=C(OC(=O)N3CCC(CC3)N4CCCCC4)C=CC2=NC5=C1CN6C5=CC7=C(COC(=O)[C@]7(O)CC)C6=O

InChI

InChIKey=GURKHSYORGJETM-WAQYZQTGSA-N

InChI=1S/C33H38N4O6.ClH/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/t33-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

Molecular Formula	C33H38N4O6
Molecular Weight	586.678
Charge	0
Count

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

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 59 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 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic carcinoma of the colon or rectum 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf	Primary		Approved 8429	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 1996

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
Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer.	2001	11419562
Factors affecting the pharmacokinetics of CPT-11: the body mass index, age and sex are independent predictors of pharmacokinetic parameters of CPT-11.	2001	11291833
Lung cancer: therapeutic options for stage IV and recurrent NSCLC.	2001	11224988
[Home chemotherapy and/or outpatient chemotherapy for patient with advanced gastric cancer].	2001 Apr	11424453
[Irinotecan (CPT-11) therapy for advanced gastric cancer].	2001 Apr	11424411
[Chemotherapy of irinotecan (CPT-11) combined with cisplatin in patients with advanced gastric cancer].	2001 Apr	11424409
A phase II trial of irinotecan (CPT-11) for unresectable biliary tree carcinoma.	2001 Apr	11398883
Human plasma carboxylesterase and butyrylcholinesterase enzyme activity: correlations with SN-38 pharmacokinetics during a prolonged infusion of irinotecan.	2001 Apr	11345644
Antitumor activity of XR5944, a novel and potent topoisomerase poison.	2001 Apr	11335793
Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan.	2001 Apr	11259359
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
26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer.	2001 Apr 2-27	11400168
[Medical treatment of pulmonary neoplasms].	2001 Feb	11294106
North Central Cancer Treatment Group--Mayo Clinic trials in colon cancer.	2001 Feb	11273589
[Weekly low dose CPT-11 for multiple lung metastases of colon cancer on an out-patient treatment: a case report].	2001 Feb	11235190
Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines.	2001 Feb	11207057
Irinotecan and chronomodulated infusion of 5-fluorouracil and folinic acid in the treatment of patients with advanced colorectal carcinoma: a phase I study.	2001 Feb 15	11241238
Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells.	2001 Feb 16	11342261
Current status of irinotecan in lung cancer.	2001 Jan	11221022
Irinotecan: summary and future directions.	2001 Jan	11221021
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
Weekly irinotecan and cisplatin in advanced non-small cell lung cancer: a multicenter phase II study.	2001 Jan	11205920
A phase I study of irinotecan in pediatric patients: a pediatric oncology group study.	2001 Jan	11205914
In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction.	2001 Jan	11205910
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
The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux.	2001 Jan 15	11212277
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
Adjuvant therapy for colon cancer: the European experience.	2001 Jan-Feb	11300039
[Irinotecan in colorectal cancer].	2001 Jan-Feb	11300023
Topoisomerase I-DNA covalent complexes in human colorectal cancer xenografts with different p53 and microsatellite instability status: relation with their sensitivity to CTP-11.	2001 Jan-Feb	11299781
Perioperative radiotherapy and concurrent radiochemotherapy in rectal cancer.	2001 Jan-Feb	11291127
New chemotherapy approaches in colorectal cancer.	2001 Jul	11429486
Control of irinotecan-induced diarrhea by octreotide after loperamide failure.	2001 Jun	11430421
Phase I-II study of irinotecan in combination with mitomycin C in patients with advanced gastrointestinal cancer.	2001 Jun	11404495
Irinotecan plus cisplatin in advanced gastric or gastroesophageal junction carcinoma.	2001 Mar	11301842
Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.	2001 Mar	11301841
Cisplatin and irinotecan in upper gastrointestinal malignancies.	2001 Mar	11301840
Optimizing chemoradiation therapy approaches to unresectable stage III non--small cell lung cancer.	2001 Mar	11224708
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
Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition.	2001 May 1	11325813
Advances in chemotherapy for small cell lung cancer: single-agent activity of newer agents.	2001 May-Jun	11419031

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 `Sat Dec 16 05:41:58 GMT 2023` Edited by `admin` on `Sat Dec 16 05:41:58 GMT 2023`
Record UNII	06X131E4OE
Record Status	`Validated (UNII)`
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Name

Type

Language

IRINOTECAN HYDROCHLORIDE ANHYDROUS

Common Name

English

(1,4'-BIPIPERIDINE)-1'-CARBOXYLIC ACID, (4S)-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, HYDROCHLORIDE (1:1)

Common Name

English

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

Common Name

English

IRINOTECAN HYDROCHLORIDE ANHYDROUS [MI]

Common Name

English

Irinotecan hydrochloride [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

74990