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
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+
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15514370
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
Sources: http://adisinsight.springer.com/drugs/800000820
Curator's Comment: Fenretinide was originally developed by Ortho-McNeil Pharmaceutical (Johnson & Johnson) for the treatment of cancer.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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220.0 nM [EC50] | |||
Target ID: CHEMBL2363069 |
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Target ID: CHEMBL2021749 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28448568 |
2.32 µM [IC50] | ||
Target ID: CHEMBL3100 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23211825 |
56.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Phase II trial of fenretinide [N-(4-hydroxyphenyl) retinamide] in myelodysplasia: possible retinoid-induced disease acceleration. | 1989 |
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Retinoid-induced apoptosis and Sp1 cleavage occur independently of transcription and require caspase activation. | 1997 Nov |
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Hydrolysis of 4-HPR to atRA occurs in vivo but is not required for retinamide-induced apoptosis. | 2003 Nov 15 |
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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 |
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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 |
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PPAR activation and decreased proliferation in oral carcinoma cells with 4-HPR. | 2005 Nov |
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Inhibitory effects of N-(4-hydrophenyl) retinamide on liver cancer and malignant melanoma cells. | 2005 Oct 7 |
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Increased level of the p67phox subunit of NADPH oxidase by 4HPR in head and neck squamous carcinoma cells. | 2005 Sep |
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Fenretinide activity in retinoid-resistant oral leukoplakia. | 2006 May 15 |
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Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells. | 2006 Sep 1 |
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Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines. | 2007 Feb |
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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 |
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Receptor tyrosine kinase inhibitors and cytotoxic drugs affect pleural mesothelioma cell proliferation: insight into EGFR and ERK1/2 as antitumor targets. | 2011 Nov 15 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21072519
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
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Edited
Fri Dec 15 15:13:36 GMT 2023
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Record UNII |
187EJ7QEXL
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Record Status |
Validated (UNII)
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Record Version |
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FDA ORPHAN DRUG |
409913
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FDA ORPHAN DRUG |
236106
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FDA ORPHAN DRUG |
615217
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FDA ORPHAN DRUG |
74193
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FDA ORPHAN DRUG |
209805
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NCI_THESAURUS |
C804
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FDA ORPHAN DRUG |
303210
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FDA ORPHAN DRUG |
621117
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FDA ORPHAN DRUG |
404013
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EU-Orphan Drug |
EU/3/06/427
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DB05076
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C1098
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FENRETINIDE
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m5295
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187EJ7QEXL
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