Fenretinide

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.

Product information

CAS Number: 65646-68-6

Molecular Weight: 391.55

Formula: C26H33NO2

Synonym:

HPR

McNR-1967

4-HP

McNR 1967

McNR1967

Fenretinide

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

Smiles: CC1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C(=O)NC1C=CC(O)=CC=1

InChiKey: AKJHMTWEGVYYSE-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+

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Fenretinide (4-HPR) exerts not just acute but also long term antitumor activity in selected T-ALL cell lines. Fenretinide inhibits DES activity in CCRF-CEM leukemia cells in a dose and time dependent manner, leading to a concomitant increase of the endogenous cellular dhCer content. Fenretinide (3 μM)-induced dhCer accumulation in both CCRF-CEM and Jurkat cells. Ceramide inhibition with fenretinide protects insulin signaling. Fenretinide prevents lipid-induced reductions in insulin-stimulated glucose uptake. Fenretinide inhibits OVCAR-5 cell proliferation and viability at concentrations higher than 1 microM, with 70-90% growth inhibition at 10 microM. Fenretinide (1 microM) significantly inhibits OVCAR-5 invasion after 3 days preincubation. Endothelial cells treated with 1 microM 4-HPR fails to form tubes, but forms small cellular aggregates.

In Vivo:

Fenretinide (4-HPR) (10 mg/kg, i.p.) selectively inhibits ceramide accumulation HFD-fed male C57Bl/6 mice. Fenretinide treatment improves glucose tolerance and insulin sensitivity as determined by both glucose and insulin tolerance tests. Addition of 25 mg/kg ketoconazole to Fenretinide in NOD/SCID mice increased 4-HPR plasma levels.

References:

1. Armstrong JL, Martin S, Illingworth NA, Jamieson D, Neilson A, Lovat PE, Redfern CP, Veal GJ. The impact of retinoic acid treatment on the sensitivity of neuroblastoma cells to fenretinide. Oncol Rep. 2012 Jan;27(1):293-8. doi: 10.3892/or.2011.1479. Epub 2011 Sep 29. PubMed PMID: 21964808.
2. Fang H, Harned TM, Kalous O, Maldonado V, Declerck YA, Reynolds CP. Synergistic Activity of Fenretinide and the Bcl-2 Family Protein Inhibitor ABT-737 against Human Neuroblastoma. Clin Cancer Res. 2011 Nov 8. [Epub ahead of print] PubMed PMID: 21933888.
3. Carr AJ, Vugler AA, Yu L, Semo M, Coffey P, Moss SE, Greenwood J. The expression of retinal cell markers in human retinal pigment epithelial cells and their augmentation by the synthetic retinoid fenretinide. Mol Vis. 2011;17:1701-15. Epub 2011 Jun 25. PubMed PMID: 21738400; PubMed Central PMCID: PMC3130725.
4. Desai KG, Mallery SR, Holpuch AS, Schwendeman SP. Development and in vitro-in vivo evaluation of fenretinide-loaded oral mucoadhesive patches for site-specific chemoprevention of oral cancer. Pharm Res. 2011 Oct;28(10):2599-609. Epub 2011 Jun 15. PubMed PMID: 21674264; PubMed Central PMCID: PMC3171589.

Products are for research use only. Not for human use.