C4 Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. [1] [2] [3] It inhibits IL-4 production by 16% in EL4 T cells stimulated with phorbol 12-myristate 13-acetate when used at a concentration of 10 μM. [1] C4 Ceramide is cytotoxic to SK-BR-3 and MCF-7/Adr breast cancer cells (IC50s = 15.9 and 19.9 μM, respectively). [2] C4 Ceramide also increases maturation and stability of cystic fibrosis transmembrane conductance regulator (CFTR) proteins bearing the F508 deletion (F508del) mutation, enhances cAMP-activated chloride secretion, and suppresses secretion of IL-8 in primary epithelial cells isolated from patients with cystic fibrosis.[3]
Reference:
[1]. Park, J., Li, Q., Chang, Y.T., et al. Inhibitory activity of a ceramide library in interleukin-4 production from activated T cells. Bioorg. Med. Chem. 13(7), 2589-2595 (2005).
[2]. Crawford, K.W., Bittman, R., Chun, J., et al. Novel ceramide analogues display selective cytotoxicity in drug-resistant breast tumor cell lines compared to normal breast epithelial cells. Cell Mol. Biol. (Noisy-le-grand) 49(7), 1017-1023 (2003).
[3]. Caohuy, H., Yang, Q., Eudy, Y., et al. Activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and serum- and glucocorticoid-induced protein kinase 1 (SGK1) by short-chain sphingolipid C4-ceramide rescues the trafficking defect of ΔF508-cystic fibrosis transmembrane conductance regulator (ΔF508-CFTR). J. Biol. Chem. 289(52), 35953-35968 (2014).