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Details

Stereochemistry ACHIRAL
Molecular Formula C26H33NO2
Molecular Weight 391.5457
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 4
Charge 0

SHOW SMILES / InChI
Structure of FENRETINIDE

SMILES

CC(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(C)=C/C(=O)NC2=CC=C(O)C=C2

InChI

InChIKey=AKJHMTWEGVYYSE-FXILSDISSA-N
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+

HIDE SMILES / InChI

Molecular Formula C26H33NO2
Molecular Weight 391.5457
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 4
Optical Activity NONE

Fenretinide (4-HPR) 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. Phase III clinical trial data has suggested that fenretinide reduces breast cancer relapse in pre-menopausal women. Fenretinide is the most studied retinoid in breast cancer chemoprevention clinical trials due to its selective accumulation in breast tissue and its favorable toxicological profile. This agent showed a significative reduction of the incidence of second breast tumors in premenopausal women confirmed after 15-year followups. Fenretinide, a drug being developed by Sirion Therapeutics, slowed the progression of advanced dry age-related macular degeneration (AMD) by 45 percent for people receiving a higher dose of the treatment in a Phase II clinical trial. Sirion has been granted a Fast Track designation for the treatment by the FDA. Fenretinide is in phase II clinical trials for the treatment of B-cell lymphoma, chronic lymphocytic leukemia. It is also in phase I clinical trials for the treatment of cystic fibrosis.

CNS Activity

Curator's Comment: Animal studies suggest that fenretinide can cross the blood-brain barrier, probably due to its lipophilicity. Clinical trials from patients with glioma indicated that 4-HPR is able to cross the blood brain barrier (BBB), suggesting its potential for the treatment of central nervous system tumors.

Originator

Curator's Comment: Fenretinide was originally developed by Ortho-McNeil Pharmaceutical (Johnson & Johnson) for the treatment of cancer.

Approval Year

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Phase II trial of fenretinide [N-(4-hydroxyphenyl) retinamide] in myelodysplasia: possible retinoid-induced disease acceleration.
1989
Retinoid-induced apoptosis and Sp1 cleavage occur independently of transcription and require caspase activation.
1997 Nov
Hydrolysis of 4-HPR to atRA occurs in vivo but is not required for retinamide-induced apoptosis.
2003 Nov 15
Nuclear retinoid receptors are involved in N-(4-hydroxyphenyl) retinamide (Fenretinide)-induced gene expression and growth inhibition in HL-60 acute myeloid leukemia cells.
2004 May
The transforming growth factor-beta family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl)retinamide.
2005 Jun 15
PPAR activation and decreased proliferation in oral carcinoma cells with 4-HPR.
2005 Nov
Inhibitory effects of N-(4-hydrophenyl) retinamide on liver cancer and malignant melanoma cells.
2005 Oct 7
Increased level of the p67phox subunit of NADPH oxidase by 4HPR in head and neck squamous carcinoma cells.
2005 Sep
Fenretinide activity in retinoid-resistant oral leukoplakia.
2006 May 15
Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells.
2006 Sep 1
Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines.
2007 Feb
p-Dodecylaminophenol derived from the synthetic retinoid, fenretinide: antitumor efficacy in vitro and in vivo against human prostate cancer and mechanism of action.
2008 Feb 1
Receptor tyrosine kinase inhibitors and cytotoxic drugs affect pleural mesothelioma cell proliferation: insight into EGFR and ERK1/2 as antitumor targets.
2011 Nov 15
Patents

Sample Use Guides

Individuals participating in the Phase II study received either one of two oral doses of fenretinide — 300 mg or 100 mg. While both doses slowed the growth of the harmful lesions associated with advanced dry AMD (also known as geographic atrophy), the higher dose was more effective.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Fenretinide inhibits OVCAR-5 cell proliferation and viability at concentrations higher than 1 uM, with 70-90% growth inhibition at 10 microM. Fenretinide (1 uM) significantly inhibits OVCAR-5 invasion after 3 days preincubation. Endothelial cells treated with 1 uM 4-HPR fails to form tubes, but forms small cellular aggregates. https://www.ncbi.nlm.nih.gov/pubmed/15816545
At the measured IC(50) of 10 uM, 4-HPR led to a 44-68% reduction in [(3)H]thymidine incorporation, a >3-fold increase in de novo ceramide levels, a 2.7-fold increase in ROS, and minor increases in markers of apoptosis in human pancreatic cancer cell lines.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:13:36 GMT 2023
Edited
by admin
on Fri Dec 15 15:13:36 GMT 2023
Record UNII
187EJ7QEXL
Record Status Validated (UNII)
Record Version
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Name Type Language
FENRETINIDE
INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
NSC-760419
Code English
MCN-R-1967
Code English
FENRETINIDE [VANDF]
Common Name English
RII RETINAMIDE
Common Name English
Fenretinide [WHO-DD]
Common Name English
N-(4-HYDROXYPHENYL)RETINAMIDE
Common Name English
RETINAMIDE, N-(4-HYDROXYPHENYL)-
Common Name English
fenretinide [INN]
Common Name English
ALL-TRANS-4'-HYDROXYRETINANILIDE
Common Name English
FENRETINIDE [MI]
Common Name English
FENRETINIDE [MART.]
Common Name English
FENRETINIDE [USAN]
Common Name English
N-(4-HYDROXYPHENYL)-ALL-TRANS-VITAMIN A AMIDE
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 409913
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 236106
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 615217
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 74193
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 209805
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
NCI_THESAURUS C804
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 303210
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 621117
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
FDA ORPHAN DRUG 404013
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
EU-Orphan Drug EU/3/06/427
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID2032005
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
DRUG BANK
DB05076
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
ChEMBL
CHEMBL7301
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
EVMPD
SUB07595MIG
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
NCI_THESAURUS
C1098
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
WIKIPEDIA
FENRETINIDE
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
PUBCHEM
5288209
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
USAN
U-72
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
CAS
65646-68-6
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
MESH
D017313
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
INN
5516
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
NSC
760419
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
SMS_ID
100000081507
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
CHEBI
42588
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
MERCK INDEX
m5295
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY Merck Index
FDA UNII
187EJ7QEXL
Created by admin on Fri Dec 15 15:13:36 GMT 2023 , Edited by admin on Fri Dec 15 15:13:36 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY