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
Structure for Fenretinide (DB05076)
- 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
Pharmacology
- Indication
Investigated for use/treatment in macular degeneration.
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
"Mechanism of fenretinide (4-HPR)-induced cell death"
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Bupivacaine. Butacaine The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Butamben. Capsaicin The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Capsaicin. Chloroprocaine The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Chloroprocaine. Cinchocaine The risk or severity of methemoglobinemia can be increased when Fenretinide is combined with Cinchocaine. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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
- 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]
- 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]
- Simeone AM, Tari AM: How retinoids regulate breast cancer cell proliferation and apoptosis. Cell Mol Life Sci. 2004 Jun;61(12):1475-84. [Article]
- External Links
- 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
Phase Status Purpose Conditions Count 3 Completed Prevention Cervical Cancer / Precancerous Conditions 1 3 Completed Treatment Bladder Cancer 1 3 Completed Treatment Breast Cancer 1 3 Terminated Prevention High Risk Cancer 1 3 Withdrawn Treatment Cognitive Functioning / Schizoaffective Disorders / Schizophrenia 1 2 Completed Prevention Breast Cancer 1 2 Completed Prevention Head And Neck Cancer 1 2 Completed Prevention Melanoma 1 2 Completed Treatment Adenocarcinoma of Prostate / Recurrent Prostate Cancer 1 2 Completed Treatment Brain and Central Nervous System Tumors 1
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
Property Value Source Water Solubility 0.00119 mg/mL ALOGPS logP 6.31 ALOGPS logP 6.15 Chemaxon logS -5.5 ALOGPS pKa (Strongest Acidic) 9.45 Chemaxon pKa (Strongest Basic) -1.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 49.33 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 128.05 m3·mol-1 Chemaxon Polarizability 47.67 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9952 Blood Brain Barrier + 0.7618 Caco-2 permeable + 0.6523 P-glycoprotein substrate Non-substrate 0.5141 P-glycoprotein inhibitor I Non-inhibitor 0.7389 P-glycoprotein inhibitor II Inhibitor 0.6346 Renal organic cation transporter Non-inhibitor 0.8486 CYP450 2C9 substrate Non-substrate 0.7527 CYP450 2D6 substrate Non-substrate 0.7217 CYP450 3A4 substrate Substrate 0.7677 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Inhibitor 0.7136 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Inhibitor 0.6897 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7917 Ames test Non AMES toxic 0.8418 Carcinogenicity Non-carcinogens 0.7868 Biodegradation Not ready biodegradable 0.9225 Rat acute toxicity 2.1836 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9585 hERG inhibition (predictor II) Non-inhibitor 0.8054
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Carriers
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- 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