Fenretinide | CAS#65646-68-6 | RAR receptor

MedKoo Cat#: 205430 | Name: Fenretinide

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Fenretinide 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.

Chemical Structure

Fenretinide

CAS#65646-68-6

Theoretical Analysis

MedKoo Cat#: 205430

Name: Fenretinide

CAS#: 65646-68-6

Chemical Formula: C26H33NO2

Exact Mass: 391.2511

Molecular Weight: 391.55

Elemental Analysis: C, 79.76; H, 8.50; N, 3.58; O, 8.17

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 950.00	Ready to ship
1g	USD 1,650.00	Ready to ship
2g	USD 2,950.00	Ready to ship
5g	USD 6,450.00	Ready to ship

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Related CAS #

No Data

Synonym

4-HPR; McNR-1967; McNR1967; McNR 1967; HPR; Fenretinide;

IUPAC/Chemical 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

InChi Key

AKJHMTWEGVYYSE-FXILSDISSA-N

InChi Code

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+

SMILES Code

O=C(NC1=CC=C(O)C=C1)/C=C(C)/C=C/C=C(C)/C=C/C2=C(C)CCCC2(C)C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Fenretinide (4-hydroxy(phenyl)retinamide; 4-HPR) (INN) is a synthetic retinoid deriverative. Retinoids are substances related to vitamin A. It has been investigated for potential use in the treatment of cancer, as well as in the treatment of cystic fibrosis, rheumatoid arthritis, acne, psoriasis, and has been found to also slow the production and accumulation of a toxin that leads to vision loss in Stargardt's patients. In cancer studies, Fenretinide treatment may cause ceramide (a wax-like substance) to build up in tumor cells and is associated with the accumulation of reactive oxygen species (ROS), resulting in cell death through apoptosis and/or necrosis. Fenretinide accumulates preferentially in fatty tissue such as the breast, which may contribute to the effectiveness of fenretinide against breast cancer. Phase III clinical trial data has suggested that fenretinide reduces breast cancer relapse in pre-menopausal women . Common side effects associated with fenretinide treatment include skin dryness and night-blindness, which is reversible upon cessation of treatment. Specific types of cancer under investigation include or have included ovarian, prostate, cervical, lung, renal, bladder, breast, glioma, skin, head and neck carcinoma, Non-Hodgkin's lymphoma, neuroblastoma, and Ewing's sarcoma. (source: http://en.wikipedia.org/wiki/Fenretinide).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R08B04

View CoA: current batch, Lot#A20T02K22

QC Data

View QC data: current batch, Lot#C20R08B04

View QC data: current batch, Lot#A20T02K22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Fenretinide (4-HPR) is a synthetic retinoid deriverative, binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death.

In vitro activity:

4-HPR inhibited OVCAR-5 cell proliferation and viability at concentrations higher than 1 microM, with 70-90% growth inhibition at 10 microM. 4-HPR (1 microM) significantly inhibited OVCAR-5 invasion after 3 days preincubation. In view of the importance of the cytoskeleton in cell motility, we examined the action of 4-HPR on the actin cytoskeleton and on FAK phosphorylation. In OVCAR-5 cells treated with 1 mM fenretinide for 3 days, actin cytoskeleton stress fibers were disrupted and FAK tyrosine phosphorylation was elevated dose-dependently. Endothelial cells treated with 1 microM 4-HPR failed to form tubes, but formed small cellular aggregates. Reference Anticancer Res. 2005 Jan-Feb;25(1A):249-53. http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=15816545

In vivo activity:

Fenretinide was shown previously to improve insulin resistance in diet-induced obese mice. The proposed mechanism was that it promotes the urinary excretion of RBP4, an adipose-derived secretagogue implicated in insulin resistance. However, subsequent studies revealed that the compound could combat hepatic steatosis and obesity in RBP4-null mice, suggesting the existence of other targets that mediated its antidiabetic actions. To determine whether fenretinide is able to target the sphingolipid synthesis pathway in vivo, lipids from soleus muscle and liver of mice 12 h after the delivery of the drug by intraperitoneal injection were measured. The single injection of the drug only slightly reduced muscle ceramide levels, but robustly increased dihydroceramide levels (Fig. 5, A and B). A similar, although less robust, effect was observed in the liver (Fig. 5, C and D). However, although fenretinide had a more pronounced effect on shorter acyl chain dihydroceramide species (e.g. C16) in muscle, it appeared to affect a longer chain species more specifically in the liver (C24). This is consistent with the recent observation that the dominant ceramide synthase in the liver (CerS2) makes predominantly longer ceramides. Altogether, these data again indicate that fenretinide modulates sphingolipid levels and are highly suggestive that it inhibits Des1 in vivo. Reference: J Biol Chem. 2012 May 18;287(21):17426-17437. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22474281/

	Solvent	mg/mL	mM
Solubility
	DMSO	130.0	332.01
	Ethanol	78.0	199.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 391.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Bikman BT, Guan Y, Shui G, Siddique MM, Holland WL, Kim JY, Fabriàs G, Wenk MR, Summers SA. Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. J Biol Chem. 2012 May 18;287(21):17426-17437. doi: 10.1074/jbc.M112.359950. Epub 2012 Apr 2. PMID: 22474281; PMCID: PMC3366851. 2. Golubkov V, Garcia A, Markland FS. Action of fenretinide (4-HPR) on ovarian cancer and endothelial cells. Anticancer Res. 2005 Jan-Feb;25(1A):249-53. PMID: 15816545.

In vivo protocol:

1: Potenza RL, Lodeserto P, Orienti I. Fenretinide in Cancer and Neurological Disease: A Two-Face Janus Molecule. Int J Mol Sci. 2022 Jul 4;23(13):7426. doi: 10.3390/ijms23137426. PMID: 35806431; PMCID: PMC9266536. 2: Ulukaya E, Wood EJ. Fenretinide and its relation to cancer. Cancer Treat Rev. 1999 Aug;25(4):229-35. doi: 10.1053/ctrv.1999.0127. PMID: 10448131. 3: Orienti I, Gentilomi GA, Farruggia G. Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment In COVID-19. Int J Mol Sci. 2020 May 27;21(11):3812. doi: 10.3390/ijms21113812. PMID: 32471278; PMCID: PMC7312074. 4: Hail N Jr, Kim HJ, Lotan R. Mechanisms of fenretinide-induced apoptosis. Apoptosis. 2006 Oct;11(10):1677-94. doi: 10.1007/s10495-006-9289-3. PMID: 16850162. 5: Cooper JP, Reynolds CP, Cho H, Kang MH. Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives. Exp Biol Med (Maywood). 2017 Jun;242(11):1178-1184. doi: 10.1177/1535370217706952. Epub 2017 Apr 21. PMID: 28429653; PMCID: PMC5478002. 6: Malone W, Perloff M, Crowell J, Sigman C, Higley H. Fenretinide: a prototype cancer prevention drug. Expert Opin Investig Drugs. 2003 Nov;12(11):1829-42. doi: 10.1517/13543784.12.11.1829. PMID: 14585058. 7: Corazzari M, Lovat PE, Oliverio S, Di Sano F, Donnorso RP, Redfern CP, Piacentini M. Fenretinide: a p53-independent way to kill cancer cells. Biochem Biophys Res Commun. 2005 Jun 10;331(3):810-5. doi: 10.1016/j.bbrc.2005.03.184. PMID: 15865936. 8: Ribatti D, Raffaghello L, Marimpietri D, Cosimo E, Montaldo PG, Nico B, Vacca A, Ponzoni M. Fenretinide as an anti-angiogenic agent in neuroblastoma. Cancer Lett. 2003 Jul 18;197(1-2):181-4. doi: 10.1016/s0304-3835(03)00105-8. PMID: 12880979. 9: Wu JM, DiPietrantonio AM, Hsieh TC. Mechanism of fenretinide (4-HPR)-induced cell death. Apoptosis. 2001 Oct;6(5):377-88. doi: 10.1023/a:1011342220621. PMID: 11483862. 10: Mody N, Mcilroy GD. The mechanisms of Fenretinide-mediated anti-cancer activity and prevention of obesity and type-2 diabetes. Biochem Pharmacol. 2014 Oct 1;91(3):277-86. doi: 10.1016/j.bcp.2014.07.012. Epub 2014 Jul 25. PMID: 25069047. 11: Cazzaniga M, Varricchio C, Montefrancesco C, Feroce I, Guerrieri-Gonzaga A. Fenretinide (4-HPR): a preventive chance for women at genetic and familial risk? J Biomed Biotechnol. 2012;2012:172897. doi: 10.1155/2012/172897. Epub 2012 Mar 5. PMID: 22500077; PMCID: PMC3303873. 12: Melis M, Tang XH, Mai K, Gudas LJ, Trasino SE. Fenretinide Reduces Intestinal Mucin-2-Positive Goblet Cells in Chronic Alcohol Abuse. Pharmacology. 2022;107(7-8):406-416. doi: 10.1159/000524386. Epub 2022 May 12. PMID: 35551126; PMCID: PMC9376936. 13: Bonanni B, Lazzeroni M, Veronesi U. Synthetic retinoid fenretinide in breast cancer chemoprevention. Expert Rev Anticancer Ther. 2007 Apr;7(4):423-32. doi: 10.1586/14737140.7.4.423. PMID: 17428163. 14: Sogno I, Venè R, Ferrari N, De Censi A, Imperatori A, Noonan DM, Tosetti F, Albini A. Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies. Crit Rev Oncol Hematol. 2010 Jul;75(1):2-14. doi: 10.1016/j.critrevonc.2009.10.007. Epub 2010 Jan 19. PMID: 20034809. 15: Makena MR, Nguyen TH, Koneru B, Hindle A, Chen WH, Verlekar DU, Kang MH, Reynolds CP. Vorinostat and fenretinide synergize in preclinical models of T-cell lymphoid malignancies. Anticancer Drugs. 2021 Jan 1;32(1):34-43. doi: 10.1097/CAD.0000000000001008. PMID: 33079733. 16: Garić D, Dumut DC, Shah J, De Sanctis JB, Radzioch D. The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide. Cell Mol Life Sci. 2020 Nov;77(21):4255-4267. doi: 10.1007/s00018-020-03530-x. Epub 2020 May 11. PMID: 32394023. 17: Raffaghello L, Pagnan G, Pastorino F, Cosimo E, Brignole C, Marimpietri D, Bogenmann E, Ponzoni M, Montaldo PG. Immunoliposomal fenretinide: a novel antitumoral drug for human neuroblastoma. Cancer Lett. 2003 Jul 18;197(1-2):151-5. doi: 10.1016/s0304-3835(03)00097-1. PMID: 12880975. 18: Torrisi R, Decensi A, Formelli F, Camerini T, De Palo G. Chemoprevention of breast cancer with fenretinide. Drugs. 2001;61(7):909-18. doi: 10.2165/00003495-200161070-00002. PMID: 11434448. 19: Lovat PE, Corazzari M, Di Sano F, Piacentini M, Redfern CP. The role of gangliosides in fenretinide-induced apoptosis of neuroblastoma. Cancer Lett. 2005 Oct 18;228(1-2):105-10. doi: 10.1016/j.canlet.2005.01.044. PMID: 15907365. 20: Pavone ME, Malpani SS, Dyson M, Kim JJ, Bulun SE. Fenretinide: A Potential Treatment for Endometriosis. Reprod Sci. 2016 Sep;23(9):1139-47. doi: 10.1177/1933719116632920. Epub 2016 Feb 25. PMID: 26919975; PMCID: PMC5933162.