Genetic studies in mice have identified sphingomyelin synthase as a novel molecular target for pharmaceutical intervention in atherosclerosis [2,4,6], obesity and insulin resistance [5]. As a result of these findings, small molecule inhibitors of sphingomyelin synthase are being investigated for their potential to provide novel therapeutics for the treatment of treatment these metabolic diseases [1,3,7].

1. Deng X, Lin F, Zhang Y, Li Y, Zhou L, Lou B, Li Y, Dong J, Ding T, Jiang X et al.. (2014) Identification of small molecule sphingomyelin synthase inhibitors. Eur J Med Chem, 73: 1-7. [PMID:24374347]

2. Jiang X-C, Yeang C, Li Z, Chakraborty M, Zhang H, Fan Y. (2009) Sphingomyelin biosynthesis: its impact on lipid metabolism and atherosclerosis. Clinical Lipidology, 4 (5): 595-609. DOI: 10.2217/clp.09.49

3. Li YL, Qi XY, Jiang H, Deng XD, Dong YP, Ding TB, Zhou L, Men P, Chu Y, Wang RX et al.. (2015) Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors. Bioorg Med Chem, 23 (18): 6173-84. [PMID:26314925]

4. Li Z, Fan Y, Liu J, Li Y, Huan C, Bui HH, Kuo MS, Park TS, Cao G, Jiang XC. (2012) Impact of sphingomyelin synthase 1 deficiency on sphingolipid metabolism and atherosclerosis in mice. Arterioscler Thromb Vasc Biol, 32 (7): 1577-84. [PMID:22580896]

5. Li Z, Zhang H, Liu J, Liang CP, Li Y, Li Y, Teitelman G, Beyer T, Bui HH, Peake DA et al.. (2011) Reducing plasma membrane sphingomyelin increases insulin sensitivity. Mol Cell Biol, 31 (20): 4205-18. [PMID:21844222]

6. Liu J, Huan C, Chakraborty M, Zhang H, Lu D, Kuo MS, Cao G, Jiang XC. (2009) Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice. Circ Res, 105 (3): 295-303. [PMID:19590047]

7. Young SA, Mina JG, Denny PW, Smith TK. (2012) Sphingolipid and ceramide homeostasis: potential therapeutic targets. Biochem Res Int, 2012: 248135. [PMID:22400113]