Fenretinide

Fenretinide is a synthetic derivative of retinoic acid (Item No. 11017) and an inhibitor of dihydroceramide desaturase (IC₅₀ = 2.32 µM).¹ It promotes the generation of reactive oxygen species (ROS), the degradation of anti-apoptotic MCL-1, and the cleavage of pro-apoptotic PKCδ.² At 5-20 µM, fenretinide selectively activates retinoic acid receptor γ (RARγ) and is reported to inhibit the growth of Caov-3, OVCAR-3, and SKOV3 ovarian cancer cells with IC₅₀ values of 3.7, 6.9, and 8.2 µM, respectively.^3,4 It also increases activity of serine palmitoyl transferase (SPT) by 1.75-fold and induces caspase-dependent apoptosis in BMEC cells (IC₅₀ = 2.4 µM).⁵ Fenretinide prevents lipid-induced reductions in insulin-stimulated glucose uptake in isolated rat soleus muscle.⁶ In vivo, fenretinide (10 mg/ml in drinking water) reduces liver and soleus muscle neutral lipid content and inhibits high-fat diet-induced increases in dihydroceramide desaturase transcription.⁶

WARNING This product is not for human or veterinary use.

1. Rahmaniyan, M., Curley, R.W., Jr., Obeid, L.M., et al. Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide. The Journal of Biological Chemisty 286(28), 24754-24764 (2011).

2. Ruvolo, V.R., Karanjeet, K.B., Schuster, T.F., et al. Role for PKCδ in fenretinide-mediated apoptosis in lymphoid leukemia cells. J. Signal Transduct. 2010, (2010).

3. Fontana, J.A., and Rishi, A.K. Classical and novel retinoids: Their targets in cancer therapy. Leukemia 16(4), 463-472 (2002).

4. Liu, S., Brown, C.W., Berlin, K.D., et al. Synthesis of flexible sulfur-containing heteroarotinoids that induce apoptosis and reactive oxygen species with discrimination between malignant and benign cells. J. Med. Chem. 47(4), 999-1007 (2004).

5. Erdreich-Epstein, A., Tran, L.B., Bowman, N.N., et al. Ceramide signaling in fenretinide-induced endothelial cell apoptosis. The Journal of Biological Chemisty 277(51), 49531-49537 (2002).

6. Bikman, B.T., Guan, Y., Shui, G., et al. Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. The Journal of Biological Chemisty 287(21), 17426-17437 (2012).