endoxifen   Click here for help

GtoPdb Ligand ID: 10203

Synonyms: N-Desmethyl-4-hydroxytamoxifen | Z-Endoxifen
PDB Ligand
Compound class: Synthetic organic
Comment: Endoxifen is the most active metabolite of tamoxifen. Endoxifen generation in vivo is performed by the cytochrome P450 (CYP) 2D6 enzyme [1,6-7,9]. In addition to its antagonistic activity at estrogen receptors, it also acts as an aromatase inhibitor [4,8].
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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.

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View interactive charts of activity data across species

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2D Structure
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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.

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Physico-chemical Properties
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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.

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Hydrogen bond acceptors 1
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 41.49
Molecular weight 373.2
XLogP 6.49
No. Lipinski's rules broken 1

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
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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/)

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Canonical SMILES CNCCOc1ccc(cc1)C(=C(c1ccccc1)CC)c1ccc(cc1)O
Isomeric SMILES CNCCOc1ccc(cc1)/C(=C(\c1ccccc1)/CC)/c1ccc(cc1)O
InChI InChI=1S/C25H27NO2/c1-3-24(19-7-5-4-6-8-19)25(20-9-13-22(27)14-10-20)21-11-15-23(16-12-21)28-18-17-26-2/h4-16,26-27H,3,17-18H2,1-2H3/b25-24-
InChI Key MHJBZVSGOZTKRH-IZHYLOQSSA-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/)
References
1. Helland T, Henne N, Bifulco E, Naume B, Borgen E, Kristensen VN, Kvaløy JT, Lash TL, Alnæs GIG, van Schaik RH et al.. (2017)
Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.
Breast Cancer Res, 19 (1): 125. [PMID:29183390]
2. Lu WJ, Desta Z, Flockhart DA. (2012)
Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer.
Breast Cancer Res Treat, 131 (2): 473-81. [PMID:21390495]
3. Lu WJ, Xu C, Pei Z, Mayhoub AS, Cushman M, Flockhart DA. (2012)
The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents.
Breast Cancer Res Treat, 133 (1): 99-109. [PMID:21814747]
4. Lv W, Liu J, Lu D, Flockhart DA, Cushman M. (2013)
Synthesis of mixed (E,Z)-, (E)-, and (Z)-norendoxifen with dual aromatase inhibitory and estrogen receptor modulatory activities.
J Med Chem, 56 (11): 4611-8. [PMID:23731360]
5. Ma J, Chu Z, Lu JBL, Liu J, Zhang Q, Liu Z, Tang D. (2018)
The Cytochrome P450 Enzyme Responsible for the Production of (Z)-Norendoxifen in vitro.
Chem Biodivers, 15 (1). [PMID:28834279]
6. Maksina AG, Daĭniak BA, Rakhmanova IV. (1988)
[Use of the spin label method for studying the structure of the brain membranes in cats with streptomycin poisoning].
Nauchnye Doki Vyss Shkoly Biol Nauki, (11): 61-4. [PMID:2852035]
7. Sanchez-Spitman A, Dezentjé V, Swen J, Moes DJAR, Böhringer S, Batman E, van Druten E, Smorenburg C, van Bochove A, Zeillemaker A et al.. (2019)
Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study.
J Clin Oncol, 37 (8): 636-646. [PMID:30676859]
8. Shagufta, Ahmad I. (2018)
Tamoxifen a pioneering drug: An update on the therapeutic potential of tamoxifen derivatives.
Eur J Med Chem, 143: 515-531. [PMID:29207335]
9. Skaar TC, Desta Z. (2018)
CYP2D6 and Endoxifen in Tamoxifen Therapy: A Tribute to David A. Flockhart.
Clin Pharmacol Ther, 103 (5): 755-757. [PMID:29473149]