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Identification
NameFenretinide
Accession NumberDB05076  (DB03922)
TypeSmall Molecule
GroupsInvestigational
Description

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.

Structure
Thumb
Synonyms
SynonymLanguageCode
4-HPRNot AvailableNot Available
4-hydroxy(phenyl)retinamideNot AvailableNot Available
N-(4-Hydroxyphenyl)All-Trans RetinamideNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number65646-68-6
WeightAverage: 391.5457
Monoisotopic: 391.251129305
Chemical FormulaC26H33NO2
InChI KeyAKJHMTWEGVYYSE-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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassRetinoids
Direct ParentRetinoids
Alternative Parents
Substituents
  • Retinoid skeleton
  • Diterpenoid
  • N-arylamide
  • Phenol
  • Benzenoid
  • Monocyclic benzene moiety
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationInvestigated for use/treatment in macular degeneration.
PharmacodynamicsNot Available
Mechanism of actionFenretinide 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity"Mechanism of fenretinide (4-HPR)-induced cell death"
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateInhibitor0.7136
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateInhibitor0.6897
CYP450 3A4 substrateInhibitor0.7959
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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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
Polarizability47.58 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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. 2007 Dec 8;. Pubmed
  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. Pubmed
  3. Simeone AM, Tari AM: How retinoids regulate breast cancer cell proliferation and apoptosis. Cell Mol Life Sci. 2004 Jun;61(12):1475-84. Pubmed
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Carriers

1. Retinol-binding protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Retinol-binding protein 4 P02753 Details

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. Pubmed
  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. Pubmed
  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. Pubmed

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Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26