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

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
Treatment of extensive stage small cell lung cancer.	2001	11224990
Lung cancer: therapeutic options for stage IV and recurrent NSCLC.	2001	11224988
A phase II trial of irinotecan (CPT-11) for unresectable biliary tree carcinoma.	2001 Apr	11398883
Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells.	2001 Feb 9	11162657
New state of the art in small-cell lung cancer.	2001 Jan	11221023
Current status of irinotecan in lung cancer.	2001 Jan	11221022
Irinotecan: summary and future directions.	2001 Jan	11221021
Docetaxel followed by gemcitabine and irinotecan in solid tumors.	2001 Jan	11221020
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
Oral fluoropyrimidine-based combination therapy in gastrointestinal cancer.	2001 Jan	11219983
Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression.	2001 Jan	11167991
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
Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer.	2001 Jan 25	11191660
Repression of cyclin B1 expression after treatment with adriamycin, but not cisplatin in human lung cancer A549 cells.	2001 Jan 26	11162602
The changing face of chemotherapy in colorectal cancer.	2001 Jan 5	11139304
Control of irinotecan-induced diarrhea by octreotide after loperamide failure.	2001 Jun	11430421
Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.	2001 Mar	11301841
Cisplatin and irinotecan in upper gastrointestinal malignancies.	2001 Mar	11301840
[A case of AFP-producing gastric cancer responding to low-dose CPT-11 and low-dose cisplatin combination chemotherapy].	2001 Mar	11265410
Topoisomerase I targeting agents in small-cell lung cancer.	2001 Mar	11177750
[Platinum compounds in cancer therapy--past, present, and future].	2001 May	11383210
Potentiation of antitumor activity of irinotecan by chemically modified oligonucleotides.	2001 May	11295057
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.

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