irinotecan   Click here for help

GtoPdb Ligand ID: 6823

Synonyms: (+)-irinotecan | biotecan | Campto® | Camptosar® | CPT-11 | irinotecan hydrochloride | Onivyde®
Approved drug PDB Ligand
irinotecan is an approved drug (FDA (1996), EMA (2016))
Compound class: Synthetic organic
Comment: Irinotecan is a semisynthetic analogue of the natural plant alkaloid camptothecin (PubChem CID 24360) which functions as a DNA replication inhibitor by binding to topoisomerase I/DNA complexes [5]. Camptothecin was first isolated from the bark and stem of Camptotheca acuminata, the Chinsese happy tree.
The PubChem CID linked here is the same isomer as recorded in irinotecan's INN record.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: irinotecan

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 114.2
Molecular weight 586.28
XLogP 4.64
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES CCC1(O)C(=O)OCc2c1cc1c3nc4ccc(cc4c(c3Cn1c2=O)CC)OC(=O)N1CCC(CC1)N1CCCCC1
Isomeric SMILES CC[C@@]1(O)C(=O)OCc2c1cc1c3nc4ccc(cc4c(c3Cn1c2=O)CC)OC(=O)N1CCC(CC1)N1CCCCC1
InChI InChI=1S/C33H38N4O6/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/t33-/m0/s1
InChI Key UWKQSNNFCGGAFS-XIFFEERXSA-N
References
1. Chrencik JE, Staker BL, Burgin AB, Pourquier P, Pommier Y, Stewart L, Redinbo MR. (2004)
Mechanisms of camptothecin resistance by human topoisomerase I mutations.
J Mol Biol, 339 (4): 773-84. [PMID:15165849]
2. Dodds HM, Haaz MC, Riou JF, Robert J, Rivory LP. (1998)
Identification of a new metabolite of CPT-11 (irinotecan): pharmacological properties and activation to SN-38.
J Pharmacol Exp Ther, 286 (1): 578-83. [PMID:9655905]
3. Kunimoto T, Nitta K, Tanaka T, Uehara N, Baba H, Takeuchi M, Yokokura T, Sawada S, Miyasaka T, Mutai M. (1987)
Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.
Cancer Res, 47 (22): 5944-7. [PMID:3664496]
4. Matsuzaki T, Yokokura T, Mutai M, Tsuruo T. (1988)
Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice.
Cancer Chemother Pharmacol, 21 (4): 308-12. [PMID:3370738]
5. Pommier Y, Redon C, Rao VA, Seiler JA, Sordet O, Takemura H, Antony S, Meng L, Liao Z, Kohlhagen G et al.. (2003)
Repair of and checkpoint response to topoisomerase I-mediated DNA damage.
Mutat Res, 532 (1-2): 173-203. [PMID:14643436]
6. Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin Jr AB, Stewart L. (2002)
The mechanism of topoisomerase I poisoning by a camptothecin analog.
Proc Natl Acad Sci USA, 99 (24): 15387-92. [PMID:12426403]
7. Tanizawa A, Fujimori A, Fujimori Y, Pommier Y. (1994)
Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials.
J Natl Cancer Inst, 86 (11): 836-42. [PMID:8182764]
8. Tsuruo T, Matsuzaki T, Matsushita M, Saito H, Yokokura T. (1988)
Antitumor effect of CPT-11, a new derivative of camptothecin, against pleiotropic drug-resistant tumors in vitro and in vivo.
Cancer Chemother Pharmacol, 21 (1): 71-4. [PMID:3342468]