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Fenretinide

PubChem CID
5288209
Structure
Fenretinide_small.png
Fenretinide_3D_Structure.png
Molecular Formula
Synonyms
  • FENRETINIDE
  • 65646-68-6
  • N-(4-Hydroxyphenyl)retinamide
  • 4-HPR
  • 4-hydroxyphenylretinamide
Molecular Weight
391.5 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2025-01-18
Description
4-hydroxyphenyl retinamide is a retinoid obtained by formal condensation of the carboxy group of all-trans retinoic acid and the anilino group of 4-hydroxyaniline. Synthetic retinoid agonist. Antiproliferative, antioxidant and anticancer agent with a long half-life in vivo. Apoptotic effects appear to be mediated by a mechanism distinct from that of 'classical' retinoids. It has a role as an antineoplastic agent and an antioxidant. It is a retinoid and a monocarboxylic acid amide. It is functionally related to an all-trans-retinoic acid.
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Fenretinide is an orally-active synthetic phenylretinamide analogue of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. Fenretinide binds to and activates retinoic acid receptors (RARs), thereby inducing cell differentiation and apoptosis in some tumor cell types. This agent also inhibits tumor growth by modulating angiogenesis-associated growth factors and their receptors and exhibits retinoid receptor-independent apoptotic properties. (NCI04)

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Fenretinide.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenamide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C26H33NO2/c1-19(11-16-24-21(3)10-7-17-26(24,4)5)8-6-9-20(2)18-25(29)27-22-12-14-23(28)15-13-22/h6,8-9,11-16,18,28H,7,10,17H2,1-5H3,(H,27,29)/b9-6+,16-11+,19-8+,20-18+
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

AKJHMTWEGVYYSE-FXILSDISSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/C(=O)NC2=CC=C(C=C2)O)/C)/C
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C26H33NO2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 NSC Number

2.3.13 Pharos Ligand ID

2.3.14 Wikidata

2.3.15 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 13-cis-Isomer Fenretinide
  • 4 Hydroxyphenylretinamide
  • 4-HPR
  • 4-Hydroxyphenylretinamide
  • Fenretinide
  • Fenretinide, 13 cis Isomer
  • Fenretinide, 13-cis-Isomer
  • Fenretinimide
  • MCN R 1967
  • MCN-R-1967
  • MCNR1967
  • N-(4-Hydroxyphenyl)-trans-Retinamide
  • N-(4-Hydroxyphenyl)retinamide

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
391.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
7.3
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
391.251129295 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
391.251129295 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
49.3 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
29
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
726
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
4
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Collision Cross Section

197.14 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111
200.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 13C NMR Spectra

1 of 2
Instrument Name
Bruker WM-360
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
Thumbnail
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2 of 2
Instrument Name
Bruker AM-270
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
Thumbnail
Thumbnail

4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 3
View All
NIST Number
104020
Library
Main library
Total Peaks
198
m/z Top Peak
109
m/z 2nd Highest
135
m/z 3rd Highest
69
Thumbnail
Thumbnail
2 of 3
View All
Source of Spectrum
W5-1989-38484-27052
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

4.2.2 MS-MS

NIST Number
1146101
Instrument Type
IT/ion trap
Collision Energy
0
Spectrum Type
MS2
Precursor Type
[M+H]+
Precursor m/z
392.2584
Total Peaks
98
m/z Top Peak
283.2
m/z 2nd Highest
255.2
m/z 3rd Highest
270.1
Thumbnail
Thumbnail

4.3 IR Spectra

4.3.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
A. B. Barua, Iowa State University, Ames, Iowa
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Instrument Name
Bruker IFS 85
Technique
KBr-Pellet
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
Thumbnail
Thumbnail

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Investigated for use/treatment in macular degeneration.

7.2 Clinical Trials

7.2.1 ClinicalTrials.gov

7.2.2 EU Clinical Trials Register

8 Pharmacology and Biochemistry

8.1 MeSH Pharmacological Classification

Anticarcinogenic Agents
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved. (See all compounds classified as Anticarcinogenic Agents.)
Antineoplastic Agents
Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

8.2 Metabolism / Metabolites

Fenretinide has known human metabolites that include (2S,3S,4S,5R)-6-[4-[[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoyl]amino]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

8.3 Mechanism of Action

Fenretinide inhibits the growth of several human cancer cell lines, acting through both retinoid-receptor-dependent and retinoid-receptor-independent mechanisms.1In vivo, fenretinide selectively accumulates in breast tissue and is particularly active in inhibiting rat mammary carcinogenesis.1 An important feature of fenretinide is its ability to inhibit cell growth through the induction of apoptosis rather than through differentiation, an effect that is strikingly different from that of vitamin A.1 In contrast to tamoxifen, which inhibits only estrogen receptor (ER)-positive tumors, fenretinide induces apoptosis in both ER-positive and ER-negative breast cancer cell lines.2 All of these properties render fenretinide an attractive candidate for breast cancer chemoprevention.

8.4 Transformations

9 Safety and Hazards

9.1 Hazards Identification

9.1.1 GHS Classification

Pictogram(s)
Irritant
Health Hazard
Signal
Danger
GHS Hazard Statements

H302 (97.7%): Harmful if swallowed [Warning Acute toxicity, oral]

H312 (95.3%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H315 (95.3%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (95.3%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H332 (95.3%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H335 (93%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H360 (97.7%): May damage fertility or the unborn child [Danger Reproductive toxicity]

Precautionary Statement Codes

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 43 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

9.1.2 Hazard Classes and Categories

Acute Tox. 4 (97.7%)

Acute Tox. 4 (95.3%)

Skin Irrit. 2 (95.3%)

Eye Irrit. 2 (95.3%)

Acute Tox. 4 (95.3%)

STOT SE 3 (93%)

Repr. 1B (97.7%)

10 Toxicity

10.1 Toxicological Information

10.1.1 Acute Effects

11 Associated Disorders and Diseases

12 Literature

12.1 Consolidated References

12.2 NLM Curated PubMed Citations

12.3 Springer Nature References

12.4 Nature Journal References

12.5 Chemical Co-Occurrences in Literature

12.6 Chemical-Gene Co-Occurrences in Literature

12.7 Chemical-Disease Co-Occurrences in Literature

13 Patents

13.1 Depositor-Supplied Patent Identifiers

13.2 WIPO PATENTSCOPE

13.3 Chemical Co-Occurrences in Patents

13.4 Chemical-Disease Co-Occurrences in Patents

13.5 Chemical-Gene Co-Occurrences in Patents

14 Interactions and Pathways

14.1 Protein Bound 3D Structures

14.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

14.2 Chemical-Target Interactions

14.3 Drug-Drug Interactions

15 Biological Test Results

15.1 BioAssay Results

16 Classification

16.1 MeSH Tree

16.2 NCI Thesaurus Tree

16.3 ChEBI Ontology

16.4 KEGG: Target-based Classification of Drugs

16.5 KEGG: Drug Groups

16.6 ChemIDplus

16.7 ChEMBL Target Tree

16.8 UN GHS Classification

16.9 NORMAN Suspect List Exchange Classification

16.10 CCSBase Classification

16.11 EPA DSSTox Classification

16.12 MolGenie Organic Chemistry Ontology

17 Information Sources

  1. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. DTP/NCI
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  5. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  6. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    (2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenamide
    https://echa.europa.eu/substance-information/-/substanceinfo/100.164.069
    (2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenamide (EC: 636-255-5)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/168890
  7. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  8. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  9. ChEBI
  10. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  11. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  12. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  13. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  14. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  15. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  16. Therapeutic Target Database (TTD)
  17. EU Clinical Trials Register
  18. Japan Chemical Substance Dictionary (Nikkaji)
  19. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  20. Metabolomics Workbench
  21. Nature Chemical Biology
  22. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  23. SpectraBase
    (2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenamide
    https://spectrabase.com/spectrum/C1UbSt12w2n
    (2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenamide
    https://spectrabase.com/spectrum/DEj79jTWyXA
    all-trans-4'-HYDROXYYRETINANILIDE
    https://spectrabase.com/spectrum/IE6LKvQYtGL
    N-(4-Hydroxy-phenyl)-retinamide
    https://spectrabase.com/spectrum/E16h94cehPU
    N-(4-Hydroxy-phenyl)-retinamide
    https://spectrabase.com/spectrum/Kt13VsUDin3
    N-(4-Hydroxy-phenyl)-retinamide
    https://spectrabase.com/spectrum/E2me0YSYPO7
  24. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    4-Hydroxyphenyl retinamide
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  25. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
    (2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide
    https://pharos.nih.gov/ligands/NMY5THLZ9P6V
  26. Protein Data Bank in Europe (PDBe)
  27. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  28. Springer Nature
  29. Wikidata
  30. Wikipedia
  31. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  32. PubChem
  33. GHS Classification (UNECE)
  34. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  35. PATENTSCOPE (WIPO)
CONTENTS