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A Ceramide-Trafficking Protein (CERT) Inhibitor
No.171(October 2016)
HPA-12 (1) is a ceramide (Cer) -trafficking inhibitor that was first discovered and synthesized by Hanada and Kobayashi et al.1,2) Ceramide is synthesized in the endoplasmic reticulum (ER) and is transported to the Golgi apparatus,3,4) where it is converted to sphingomyelin, by means of the ceramide transport protein (CERT).5) 1 inhibits the CERT, and has been used as a CERT inhibitor in various biological science studies.6) For example, 1 possesses antiviral and antibacterial properties against the growth of hepatitis C virus (HCV) and the obligate intracellular bacteria Chlamydiae in cultured human cells.6a,d,e) In addition, the CERT inhibition results in resensitization of cancer cells to chemotherapeutic agents such as paclitaxel.6b) Therefore, the inhibition of CERT may represent medical strategies, such as anti-infective and anticancer chemotherapy.
References
- 1)Identification of a specific stereoisomer of HPA-12 as an inhibitor of Cer transport
- 2)Revising the stereochemistry and large-scale synthesis of HPA-12
- 3)Identification of CERT
- 4)The latest review on CERT
- 5)Showing HPA-12 as an antagonist of a ceramide transfer protein
- 6)Applications of HPA-12 as an inhibitor of Cer transport
- a) H. Sakamoto, K. Okamoto, M. Aoki, H. Kato, A. Katsume, A. Ohta, T. Tsukuda, N. Shimma, Y. Aoki, M. Arisawa, M. Kohara, M. Sudoh, Nat. Chem. Biol. 2005, 1, 333.
- b)C. Swanton, M. Marani, O. Pardo, P. H. Warne, G. Kelly, E. Sahai, F. Elustondo, J. Chang, J. Temple, A. A. Ahmed, J. D. Brenton, J. Downward, B. Nicke, Cancer Cell 2007, 11, 498.
- c)A. Charruyer, S. M. Bell, M. Kawano, S. Douangpanya, T.-Y. Yen, B. A. Macher, K. Kumagai, K. Hanada, W. M. Holleran, Y. Uchida, J. Biol. Chem. 2008, 283, 16682.
- d)H. Aizaki, K. Morikawa, M. Fukasawa, H. Hara, Y. Inoue, H. Tani, K. Saito, M. Nishijima, K. Hanada, Y. Matsuura, M. M. C. Lai, T. Miyamura, T. Wakita, T. Suzuki, J. Virol. 2008, 82, 5715.
- e)C. A. Elwell, S. Jiang, J. H. Kim, A. Lee, T. Wittmann, K. Hanada, P. Melancon, J. N. Engel, PLoS Pathog. 2011, 7, e1002198.
- f)T. Makiyama, H. Nakamura, N. Nagasaka, H. Yamashita, T. Honda, N. Yamaguchi, A. Nishida, T. Murayama, Traffic 2015, 16, 476.
- a) H. Sakamoto, K. Okamoto, M. Aoki, H. Kato, A. Katsume, A. Ohta, T. Tsukuda, N. Shimma, Y. Aoki, M. Arisawa, M. Kohara, M. Sudoh, Nat. Chem. Biol. 2005, 1, 333.
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