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.
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: irinotecan

irinotecan is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
Preclinical studies of irinotecan focussed on its anti-tumour effects [3-4,8], and we have been unable to find affinity data to substantiate its molecular mechanism of action. We map the primary target as DNA topoisomerase I (TOP1) for data metrics purposes, based on irinotecan's similarity to camptothecin and topotecan, which have both been reported in crystal structures with TOP1/DNA complexes (see Protein Data Bank entries 1RRJ [1] and 1K4T [6]).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
DNA topoisomerase I Primary target of this compound Bt Inhibitor Inhibition - - - 2,7
⤷ [2,7]
Description: Effect of irinotecan on topoisomerase I-mediated DNA cleavage