Myriocin is an amino fatty acid antibiotic derived from certain thermophylic fungi, in this case Mycelia sterilia. It is a potent immunosuppressant having 10- to 100-fold more activity than cyclosporin A.[1] Myriocin is a potent inhibitor of serine palmitoyltransferase (Ki = 0.28 nM), the enzyme that catalyzes the first step of sphingolipid biosynthesis. [2] It disrupts substratum adhesion of melanoma cells.[3] It also suppresses cell proliferation in the murine cytotoxic T cell line CTLL-2 (IC50 = 15 nM) via apoptosis.[2],[4] Myriocin suppresses replication of the hepatitis C virus in a murine model.[5]
Myriocin是从某些热耐受真菌中提取的氨基脂肪酸类抗生素，具有10-至100倍于环孢霉素A的免疫抑制作用[1]。Myriocin是丝氨酰基转移酶（Ki = 0.28 nM）的强效抑制剂，该酶催化鞘磷脂生物合成的第一步[2]。它可以破坏黑色素瘤细胞的底物附着[3]。Myriocin还通过凋亡途径抑制小鼠细胞毒性T细胞系CTLL-2的增殖（IC50 = 15 nM）[2]，并抑制乙型肝炎病毒在小鼠模型中的复制[5]。
Reference:
[1]. Fujita, T., Inoue, K., Yamamoto, S., et al. Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. Journal of Antibiotics 47, 208-215 (1994).
[2]. Miyake, Y., Kozutsumi, Y., Nakamura, S., et al. Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin. Biochemical and Biophysical Research Communications 211(2), 396-403 (1995).
[3]. Hidari, K.I.P.J., Ichikawa, S., Fujita, T., et al. Complete removal of sphingolipids from the plasma membrane disrupts cell to substratum adhesion of mouse melanoma cells. The Journal of Biological Chemisty 271(24), 14636-14641 (1996).
[4]. Nakamura, S., Kozutsumi, Y., Sun, Y., et al. Dual roles of sphingolipids in signaling of the escape from and onset of apoptosis in a mouse cytotoxic T-cell line, CTLL-2. The Journal of Biological Chemisty 271, 1255-1257 (1996).
[5]. Umehara, T., Sudoh, M., Yasui, F., et al. Serine palmitoyltransferase inhibitor suppresses HCV replication in a mouse model. Biochemical and Biophysical Research Communications 346, 67-73 (2006).