NAV

Fenretinide

Identification

Generic Name
Fenretinide
DrugBank Accession Number
DB05076
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 391.5457
Monoisotopic: 391.251129305
Chemical Formula
C26H33NO2
Synonyms
  • 4-HPR
  • 4-hydroxy(phenyl)retinamide
  • 4-hydroxyphenyl retinamide
  • Fenretinida
  • Fenretinide
  • Fenretinidum
  • N-(4-hydroxyphenyl)all-trans retinamide
External IDs
  • LAU-7b
  • MCN-R-1967
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Pharmacology

Indication

Investigated for use/treatment in macular degeneration.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

"Mechanism of fenretinide (4-HPR)-induced cell death"

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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AmbroxolThe risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Benzyl alcohol.
BupivacaineThe risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Bupivacaine.
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Retinoids
Direct Parent
Retinoids
Alternative Parents
Diterpenoids / Anilides / N-arylamides / 1-hydroxy-2-unsubstituted benzenoids / Secondary carboxylic acid amides / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
1-hydroxy-2-unsubstituted benzenoid / Anilide / Aromatic homomonocyclic compound / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Diterpenoid / Hydrocarbon derivative / Monocyclic benzene moiety
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid amide, retinoid (CHEBI:42588)
Affected organisms
Not Available

Chemical Identifiers

UNII
187EJ7QEXL
CAS number
65646-68-6
InChI Key
AKJHMTWEGVYYSE-FXILSDISSA-N
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+
IUPAC Name
(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
SMILES
C\C(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C/C(=O)NC1=CC=C(O)C=C1

References

General References
  1. Formelli F, Cavadini E, Luksch R, Garaventa A, Villani MG, Appierto V, Persiani S: Pharmacokinetics of oral fenretinide in neuroblastoma patients: indications for optimal dose and dosing schedule also with respect to the active metabolite 4-oxo-fenretinide. Cancer Chemother Pharmacol. 2008 Sep;62(4):655-65. Epub 2007 Dec 8. [Article]
  2. Takahashi N, Watanabe Y, Maitani Y, Yamauchi T, Higashiyama K, Ohba T: p-Dodecylaminophenol derived from the synthetic retinoid, fenretinide: antitumor efficacy in vitro and in vivo against human prostate cancer and mechanism of action. Int J Cancer. 2008 Feb 1;122(3):689-98. [Article]
  3. Simeone AM, Tari AM: How retinoids regulate breast cancer cell proliferation and apoptosis. Cell Mol Life Sci. 2004 Jun;61(12):1475-84. [Article]
KEGG Drug
D04162
PubChem Compound
5288209
PubChem Substance
175426938
ChemSpider
4450416
BindingDB
50092055
ChEBI
42588
ChEMBL
CHEMBL7301
ZINC
ZINC000003871023
PDBe Ligand
FEN
Wikipedia
Fenretinide
PDB Entries
1fel

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3CompletedPreventionCervical Cancer / Precancerous Conditions1
3CompletedTreatmentBladder Cancer1
3CompletedTreatmentBreast Cancer1
3TerminatedPreventionHigh Risk Cancer1
3WithdrawnTreatmentCognitive Functioning / Schizoaffective Disorders / Schizophrenia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00119 mg/mLALOGPS
logP6.31ALOGPS
logP6.15Chemaxon
logS-5.5ALOGPS
pKa (Strongest Acidic)9.45Chemaxon
pKa (Strongest Basic)-1.2Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area49.33 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity128.05 m3·mol-1Chemaxon
Polarizability47.67 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.7618
Caco-2 permeable+0.6523
P-glycoprotein substrateNon-substrate0.5141
P-glycoprotein inhibitor INon-inhibitor0.7389
P-glycoprotein inhibitor IIInhibitor0.6346
Renal organic cation transporterNon-inhibitor0.8486
CYP450 2C9 substrateNon-substrate0.7527
CYP450 2D6 substrateNon-substrate0.7217
CYP450 3A4 substrateSubstrate0.7677
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorInhibitor0.7136
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.6897
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7917
Ames testNon AMES toxic0.8418
CarcinogenicityNon-carcinogens0.7868
BiodegradationNot ready biodegradable0.9225
Rat acute toxicity2.1836 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9585
hERG inhibition (predictor II)Non-inhibitor0.8054
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-0169000000-a57b2adeae58f18330a8
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-05o3-0593000000-0e40a8e54c38c6ba2769
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4l-2965000000-8522d39c79f15fca563a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0923000000-858fe6181da13b9f7534
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052u-2953000000-f926caba0a5dda4f7683
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0aw9-0911000000-64af8fe6fc1d5baddab7
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-225.1573165
predicted
DarkChem Lite v0.1.0
[M-H]-218.05676
predicted
DeepCCS 1.0 (2019)
[M+H]+223.7544165
predicted
DarkChem Lite v0.1.0
[M+H]+220.41478
predicted
DeepCCS 1.0 (2019)
[M+Na]+223.6777165
predicted
DarkChem Lite v0.1.0
[M+Na]+227.12993
predicted
DeepCCS 1.0 (2019)

Carriers

Details1. Retinol-binding protein 4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Retinol transporter activity
Specific Function
Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.
Gene Name
RBP4
Uniprot ID
P02753
Uniprot Name
Retinol-binding protein 4
Molecular Weight
23009.8 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51