FENRETINIDE

Investigational

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 Search

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

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/fenretinide | https://www.ncbi.nlm.nih.gov/pubmed/22500077 | https://www.ncbi.nlm.nih.gov/pubmed/25069047

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Retinoic acid receptor beta 18 Target ID: CHEMBL2008 Sources: https://tools.thermofisher.com/content/sfs/manuals/RARbeta_valpak_with_DAcells.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/28448568	Agonist 2752	220.0 nM [EC50]
Retinoic acid receptor 8 Target ID: CHEMBL2363069 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26592777 \| https://www.bocsci.com/fenretinide-cas-65646-68-6-item-84-74597.html	Agonist 2752
Sphingolipid delta(4)-desaturase DES1 5 Target ID: CHEMBL2021749 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28448568	Inhibitor 8504	2.32 µM [IC50]
Plasma retinol-binding protein 1 Target ID: CHEMBL3100 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23211825	Inhibitor 8504	56.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Dry age-related macular degeneration 1 Sources: http://www.blindness.org/treatments/promising-drug-slows-progression-dry-amd-45-percent	Primary	Phase II 1147	Unknown Approved Use Unknown
Cervical cancer 40 Sources: https://clinicaltrials.gov/ct2/show/NCT00003075	Primary	Phase III 665	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://clinicaltrials.gov/ct2/show/NCT00002646	Primary	Phase III 665	Unknown Approved Use Unknown
Bladder cancer 16 Sources: https://clinicaltrials.gov/ct2/show/NCT00004154	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
7.3 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16034523	1800 mg/m² 2 times / day multiple, oral dose: 1800 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: [NO STEREO] NSC-LSC-1\|[NO STEREO] PACLITAXEL	[NO STEREO] NSC-LSC-1\|[NO STEREO] PACLITAXEL	FENRETINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
60.3 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16034523	1800 mg/m² 2 times / day multiple, oral dose: 1800 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: [NO STEREO] NSC-LSC-1\|[NO STEREO] PACLITAXEL	[NO STEREO] NSC-LSC-1\|[NO STEREO] PACLITAXEL	FENRETINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16034523	1800 mg/m² 2 times / day multiple, oral dose: 1800 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: [NO STEREO] NSC-LSC-1\|[NO STEREO] PACLITAXEL	[NO STEREO] NSC-LSC-1\|[NO STEREO] PACLITAXEL	FENRETINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003R1Q	https://www.1pchem.com/search?query=1P003R1Q
A2B Chem	AB74222	http://a2bchem.com/prod/AB74222
AChemBlock	O33734	http://www.achemblock.com/catalogsearch/result/?q=O33734
AK Scientific	3670AH	https://aksci.com/item_detail.php?cat=3670AH
Ambeed	A129384	http://www.ambeed.com/search/Search.html?keyword=A129384
AOBIOUS INC	AOB6402	http://aobious.com/aobious/search?search_query=AOB6402
Apollo Scientific	BIFK0053	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIFK0053&product_group=%25&search_fieldname=header_search
AstaTech	41260	http://astatechinc.com/CPSResult.php?CRNO=41260
BLD Pharm	BD97993	http://www.bldpharm.com/search/Search.html?keyword=BD97993
BOC Sciences	65646-68-6	http://www.bocsci.com/description.asp?cas=65646-68-6
Cayman Chemical	17688	http://www.caymanchem.com/app/template/Product.vm/catalog/17688
Chem Scene	CS-0789	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0789
ChemShuttle	153206	https://www.chemshuttle.com/catalogsearch/result/?q=153206
eMolecules	539366	https://orderbb.emolecules.com/search/#?query=539366
eNovation Chemicals	D509198	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D509198&searchbtn.x=0&searchbtn.y=0
Fluorochem	468334	http://www.fluorochem.co.uk/Products/Product?code=468334
Hairui	HR119676	http://www.hairuichem.com/en/product/search.do?q=HR119676
KeyOrganics	AS-59667	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-59667
Lab Network	LN01285354	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01285354
Lab Seeker	SC-76490	http://www.labseeker.com/search.php?keywords=SC-76490&category=0
LabSeeker	SC-76490	http://www.labseeker.com/search.php?keywords=SC-76490&category=0
mcule	MCULE-3137409516	https://mcule.com/MCULE-3137409516/
MedChem Express	HY-15373	https://www.medchemexpress.com/search.html?q=HY-15373&ft=&fa=&fp=
Molnova	M15496	https://www.molnova.com/en/serch-list.html?keywords=M15496
MolPort	MolPort-003-666-842	https://www.molport.com/shop/molecule-link/MolPort-003-666-842
MuseChem	I004475	https://www.musechem.com/product/I004475.html
PI Chemicals	PI-15713	http://www.pipharm.com/catalog_products/PI-15713.html
Selleck Chemicals	S5233	http://www.selleckchem.com/search.html?searchDTO.searchParam=S5233
ShangHai Biochempartner	BCP06908	http://www.biochempartner.com/search_BCP06908
TargetMol	T1872	https://www.targetmol.com/search?keyword=T1872
Tocris	1396	https://www.tocris.com/search.php?Type=QuickSearch&Value=1396
Toronto Research Chemicals	F250000	https://www.trc-canada.com/product-detail/?CatNum=F250000

PubMed

Title	Date	PubMed
Receptor tyrosine kinase inhibitors and cytotoxic drugs affect pleural mesothelioma cell proliferation: insight into EGFR and ERK1/2 as antitumor targets.	2011-11-15	21787763
Fenretinide derivatives act as disrupters of interactions of serum retinol binding protein (sRBP) with transthyretin and the sRBP receptor.	2011-07-14	21591606
Enrichment of Nur77 mediated by retinoic acid receptor β leads to apoptosis of human hepatocellular carcinoma cells induced by fenretinide and histone deacetylase inhibitors.	2011-03	21319187
HIF-1α-dependent autophagy protects HeLa cells from fenretinide (4-HPR)-induced apoptosis in hypoxia.	2010-11	20637870
Targeting GRP78 to enhance melanoma cell death.	2010-10	20546536
Induction and intracellular localization of Nur77 dictate fenretinide-induced apoptosis of human liver cancer cells.	2010-04-01	19912993
Regulation of endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells.	2010-02-26	20022965
Pharmacokinetics of oral fenretinide in neuroblastoma patients: indications for optimal dose and dosing schedule also with respect to the active metabolite 4-oxo-fenretinide.	2008-09	18066548
p-Dodecylaminophenol derived from the synthetic retinoid, fenretinide: antitumor efficacy in vitro and in vivo against human prostate cancer and mechanism of action.	2008-02-01	17955489
Novel retinoic acid metabolism blocking agents have potent inhibitory activities on human breast cancer cells and tumour growth.	2007-04-23	17387344
Targeting homeostatic mechanisms of endoplasmic reticulum stress to increase susceptibility of cancer cells to fenretinide-induced apoptosis: the role of stress proteins ERdj5 and ERp57.	2007-04-10	17353921
Fenretinide up-regulates DR5/TRAIL-R2 expression via the induction of the transcription factor CHOP and combined treatment with fenretinide and TRAIL induces synergistic apoptosis in colon cancer cell lines.	2007-03	17273769
Role of Noxa in p53-independent fenretinide-induced apoptosis of neuroectodermal tumours.	2007-03	17216584
Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines.	2007-02	16950796
Anti-proliferative activity of fenretinide in human hepatoma cells in vitro and in vivo.	2007-01	17159502
N-(4-hydroxyphenyl)retinamide induces apoptosis in human retinal pigment epithelial cells: retinoic acid receptors regulate apoptosis, reactive oxygen species generation, and the expression of heme oxygenase-1 and Gadd153.	2006-12	16972258
Fenretinide-induced neuronal differentiation of ARPE-19 human retinal pigment epithelial cells is associated with the differential expression of Hsp70, 14-3-3, pax-6, tubulin beta-III, NSE, and bag-1 proteins.	2006-11-01	17110918
Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR.	2006-10-01	16671099
Mechanism of 4-HPR-induced apoptosis in glioma cells: evidences suggesting role of mitochondrial-mediated pathway and endoplasmic reticulum stress.	2006-10	16675469
Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells.	2006-09-01	16720286
4-HPR modulates gene expression in ovarian cells.	2006-09-01	16570282
Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells.	2006-07	16632523
Fenretinide activity in retinoid-resistant oral leukoplakia.	2006-05-15	16707609
N-(4-hydroxyphenyl)retinamide-induced apoptosis triggered by reactive oxygen species is mediated by activation of MAPKs in head and neck squamous carcinoma cells.	2006-05-04	16407847
4-oxo-fenretinide, a recently identified fenretinide metabolite, induces marked G2-M cell cycle arrest and apoptosis in fenretinide-sensitive and fenretinide-resistant cell lines.	2006-03-15	16540676
Clinical trials with retinoids for breast cancer chemoprevention.	2006-03	16601279
The CLN9 protein, a regulator of dihydroceramide synthase.	2006-02-03	16303764
Chemoprevention of skin carcinogenesis by phenylretinamides: retinoid receptor-independent tumor suppression.	2006-02-01	16467112
Cholecalciferol (vitamin D3) and the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) are synergistic for chemoprevention of prostate cancer.	2006	17024972
BBC3 mediates fenretinide-induced cell death in neuroblastoma.	2005-12-01	16091745
Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: a potential therapy for treatment of lipofuscin-based retinal diseases.	2005-12	16303925
Cervical chromosome 9 polysomy: validation and use as a surrogate endpoint biomarker in a 4-HPR chemoprevention trial.	2005-12	16154183
PPAR activation and decreased proliferation in oral carcinoma cells with 4-HPR.	2005-11	16274795
Cyclooxygenase-2 protein reduces tamoxifen and N-(4-hydroxyphenyl)retinamide inhibitory effects in breast cancer cells.	2005-11	16127422
N-(4-hydroxyphenyl)retinamide inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of I(kappa)B(alpha) kinase and nuclear factor-kappaB-regulated gene products.	2005-10-15	16230421
Inhibitory effects of N-(4-hydrophenyl) retinamide on liver cancer and malignant melanoma cells.	2005-10-07	16270382
Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists.	2005-10	16133793
Retinamide-induced apoptosis in glioblastomas is associated with down-regulation of Bcl-xL and Bcl-2 proteins.	2005-09	16187019
Increased level of the p67phox subunit of NADPH oxidase by 4HPR in head and neck squamous carcinoma cells.	2005-09	16077929
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.	2005-06-15	15958647
[The role of reactive oxygen species in N-[4-hydroxyphenyl] retinamide induced apoptosis in bladder cancer cell lineT24].	2005-06	16124896
Expression of gastrointestinal glutathione peroxidase is inversely correlated to the presence of hepatitis C virus subgenomic RNA in human liver cells.	2005-03-11	15623509
Induction of apoptosis in primary meningioma cultures by fenretinide.	2005-02-15	15735044
Induction of reactive oxygen species renders mutant and wild-type K-ras pancreatic carcinoma cells susceptible to Ad.mda-7-induced apoptosis.	2005-01-20	15580305
Breast cancer progression in MCF10A series of cell lines is associated with alterations in retinoic acid and retinoid X receptors and with differential response to retinoids.	2004-10	15375546
Retinoid-induced apoptosis and Sp1 cleavage occur independently of transcription and require caspase activation.	1997-11	9343396
Regulation of apoptosis induced by the retinoid N-(4-hydroxyphenyl) retinamide and effect of deregulated bcl-2.	1995-01-15	7811993
Phase II trial of fenretinide [N-(4-hydroxyphenyl) retinamide] in myelodysplasia: possible retinoid-induced disease acceleration.	1989	2523991
Abnormal retinal function associated with fenretinide, a synthetic retinoid.	1986-01	2935125
Subacute toxicity of all-trans- and 13-cis-isomers of N-ethyl retinamide, N-2-hydroxyethyl retinamide, and N-4-hydroxyphenyl retinamide.	1983-09-15	6226123

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 17:50:52 GMT 2025` Edited by `admin` on `Mon Mar 31 17:50:52 GMT 2025`
Record UNII	187EJ7QEXL
Record Status	`Validated (UNII)`
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Name

Type

Language

MCN-R-1967

Preferred Name

English

FENRETINIDE

Official Name

English

NSC-760419

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