Synonym
Thermozymocidin; ISP-I; ISP-1; Myriocin;
IUPAC/Chemical Name
(2R,3R,4S,E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoicos-6-enoic acid
InChi Key
ZZIKIHCNFWXKDY-ANSFIGKPSA-N
InChi Code
InChI=1S/C21H39NO6/c1-2-3-4-10-13-17(24)14-11-8-6-5-7-9-12-15-18(25)19(26)21(22,16-23)20(27)28/h9,12,18-19,23,25-26H,2-8,10-11,13-16,22H2,1H3,(H,27,28)/b12-9+/t18-,19-,21+/m0/s1
SMILES Code
CCCCCCC(CCCCCC/C=C/C[C@H](O)[C@H](O)[C@@](CO)(N)C(O)=O)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Myriocin (Thermozymocidin) is a potent inhibitor of serine-palmitoyl-transferase (SPT). Myriocin suppresses replication of both the subgenomic HCV-1b replicon and the JFH-1 strain of genotype 2a infectious HCV, with an IC50 of 3.5 µg/mL for inhibiting HCV infection.
In vitro activity:
Using the HCV cell culture system, this study investigated the effect of myriocin, a sphingomyelin synthesis inhibitor, on HCV replication. Myriocin suppressed replication of both a genotype 1b subgenomic HCV replicon (Huh7/Rep-Feo) and genotype 2a infectious HCV (JFH-1 HCV) in a dose-dependent manner (for subgenomic HCV-1b, maximum of 79% at 1000 nmol/L; for genomic HCV-2a, maximum of 40% at 1000 nmol/L).
Reference: J Infect Dis. 2008 Feb 1;197(3):361-70. https://pubmed.ncbi.nlm.nih.gov/18248300/
In vivo activity:
To evaluate the biological effects of myriocin in vivo, we investigated the levels of free sphingoid bases and expression of selected genes regulating cell growth in mouse liver. Male Balb/c mice, weighing 22 g were injected intraperitoneally with myriocin at 0, 0.1, 0.3, and 1.0 mg kg(-1) body weight daily for 5 days. Results showed that myriocin blocked de novo synthesis of sphingolipids in vivo by SPT inhibition and induced c-myc expression in liver.
Reference: Mycopathologia. 2004 Apr;157(3):339-47. https://pubmed.ncbi.nlm.nih.gov/15180163/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
4.4 |
10.83 |
| Methanol |
2.0 |
4.98 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
401.54
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. He L, Liu Y, Xu J, Li J, Cheng G, Cai J, Dang J, Yu M, Wang W, Duan W, Liu K. Inhibitory Effects of Myriocin on Non-Enzymatic Glycation of Bovine Serum Albumin. Molecules. 2022 Oct 18;27(20):6995. doi: 10.3390/molecules27206995. PMID: 36296589; PMCID: PMC9607541.
2. Amemiya F, Maekawa S, Itakura Y, Kanayama A, Matsui A, Takano S, Yamaguchi T, Itakura J, Kitamura T, Inoue T, Sakamoto M, Yamauchi K, Okada S, Yamashita A, Sakamoto N, Itoh M, Enomoto N. Targeting lipid metabolism in the treatment of hepatitis C virus infection. J Infect Dis. 2008 Feb 1;197(3):361-70. doi: 10.1086/525287. PMID: 18248300.
3. Yalcin EB, Tong M, Homans C, de la Monte SM. Myriocin Treatment Reverses Alcohol-Induced Alterations in Polyunsaturated Fatty Acid-Containing Phospholipid Expression in the Liver. Nutr Metab Insights. 2022 Feb 28;15:11786388221082012. doi: 10.1177/11786388221082012. PMID: 35250275; PMCID: PMC8891894.
4. He Q, Johnson VJ, Osuchowski MF, Sharma RP. Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes induction of c-myc in mouse liver. Mycopathologia. 2004 Apr;157(3):339-47. doi: 10.1023/b:myco.0000024182.04140.95. PMID: 15180163.
In vitro protocol:
1. He L, Liu Y, Xu J, Li J, Cheng G, Cai J, Dang J, Yu M, Wang W, Duan W, Liu K. Inhibitory Effects of Myriocin on Non-Enzymatic Glycation of Bovine Serum Albumin. Molecules. 2022 Oct 18;27(20):6995. doi: 10.3390/molecules27206995. PMID: 36296589; PMCID: PMC9607541.
2. Amemiya F, Maekawa S, Itakura Y, Kanayama A, Matsui A, Takano S, Yamaguchi T, Itakura J, Kitamura T, Inoue T, Sakamoto M, Yamauchi K, Okada S, Yamashita A, Sakamoto N, Itoh M, Enomoto N. Targeting lipid metabolism in the treatment of hepatitis C virus infection. J Infect Dis. 2008 Feb 1;197(3):361-70. doi: 10.1086/525287. PMID: 18248300.
In vivo protocol:
1. Yalcin EB, Tong M, Homans C, de la Monte SM. Myriocin Treatment Reverses Alcohol-Induced Alterations in Polyunsaturated Fatty Acid-Containing Phospholipid Expression in the Liver. Nutr Metab Insights. 2022 Feb 28;15:11786388221082012. doi: 10.1177/11786388221082012. PMID: 35250275; PMCID: PMC8891894.
2. He Q, Johnson VJ, Osuchowski MF, Sharma RP. Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes induction of c-myc in mouse liver. Mycopathologia. 2004 Apr;157(3):339-47. doi: 10.1023/b:myco.0000024182.04140.95. PMID: 15180163.
1: Aburasayn H, Al Batran R, Ussher JR. Targeting ceramide metabolism in obesity. Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2):E423-35. doi: 10.1152/ajpendo.00133.2016. Epub 2016 Jul 5. Review. PubMed PMID: 27382035.
2: Zécri FJ. From Natural Product to the First Oral Treatment for Multiple Sclerosis: The Discovery of FTY720 (Gilenya™)? Curr Opin Chem Biol. 2016 Jun;32:60-6. doi: 10.1016/j.cbpa.2016.04.014. Epub 2016 May 31. Review. PubMed PMID: 27258401.
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4: Lo HC, Hsieh C, Lin FY, Hsu TH. A Systematic Review of the Mysterious Caterpillar Fungus Ophiocordyceps sinensis in Dong-ChongXiaCao ( Dōng Chóng Xià Cǎo) and Related Bioactive Ingredients. J Tradit Complement Med. 2013 Jan;3(1):16-32. doi: 10.4103/2225-4110.106538. Review. PubMed PMID: 24716152; PubMed Central PMCID: PMC3924981.
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6: Podbielska M, Krotkiewski H, Hogan EL. Signaling and regulatory functions of bioactive sphingolipids as therapeutic targets in multiple sclerosis. Neurochem Res. 2012 Jun;37(6):1154-69. doi: 10.1007/s11064-012-0728-y. Epub 2012 Mar 27. Review. PubMed PMID: 22451227.
7: Jiang XC, Goldberg IJ, Park TS. Sphingolipids and cardiovascular diseases: lipoprotein metabolism, atherosclerosis and cardiomyopathy. Adv Exp Med Biol. 2011;721:19-39. doi: 10.1007/978-1-4614-0650-1_2. Review. PubMed PMID: 21910080.
8: Yeung BK. Natural product drug discovery: the successful optimization of ISP-1 and halichondrin B. Curr Opin Chem Biol. 2011 Aug;15(4):523-8. doi: 10.1016/j.cbpa.2011.05.019. Epub 2011 Jun 22. Review. PubMed PMID: 21684798.
9: Strader CR, Pearce CJ, Oberlies NH. Fingolimod (FTY720): a recently approved multiple sclerosis drug based on a fungal secondary metabolite. J Nat Prod. 2011 Apr 25;74(4):900-7. doi: 10.1021/np2000528. Epub 2011 Apr 1. Review. PubMed PMID: 21456524.
10: Friedrich FW, Eschenhagen T. [Fingolimod - a new immunomodulator]. Dtsch Med Wochenschr. 2009 Oct;134(42):2127-31. doi: 10.1055/s-0029-1241903. Epub 2009 Oct 6. Review. German. PubMed PMID: 19809964.
11: Chiba K. [New therapeutic approach for autoimmune diseases by the sphingosine 1-phosphate receptor modulator, fingolimod (FTY720)]. Yakugaku Zasshi. 2009 Jun;129(6):655-65. Review. Japanese. PubMed PMID: 19483408.
12: Chiba K. [A new therapeutic approach for autoimmune diseases by the sphingosine 1-phosphate receptor modulator, fingolimod (FTY720)]. Nihon Rinsho Meneki Gakkai Kaishi. 2009 Apr;32(2):92-101. Review. Japanese. PubMed PMID: 19404007.
13: Hiestand PC, Rausch M, Meier DP, Foster CA. Ascomycete derivative to MS therapeutic: S1P receptor modulator FTY720. Prog Drug Res. 2008;66:361, 363-81. Review. PubMed PMID: 18416311.
14: Bismuth J, Lin P, Yao Q, Chen C. Ceramide: a common pathway for atherosclerosis? Atherosclerosis. 2008 Feb;196(2):497-504. Epub 2007 Oct 25. Review. PubMed PMID: 17963772; PubMed Central PMCID: PMC2924671.
15: Baumruker T, Billich A, Brinkmann V. FTY720, an immunomodulatory sphingolipid mimetic: translation of a novel mechanism into clinical benefit in multiple sclerosis. Expert Opin Investig Drugs. 2007 Mar;16(3):283-9. Review. PubMed PMID: 17302523.
16: Chiba K, Matsuyuki H, Maeda Y, Sugahara K. Role of sphingosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus. Cell Mol Immunol. 2006 Feb;3(1):11-9. Review. PubMed PMID: 16549044.
17: Nishikido M, Kanekake H, Harada T. [Molecular action mechanisms of the therapeutic agents for kidney diseases: Immunosuppressants]. Nihon Rinsho. 2006 Feb;64 Suppl 2:634-8. Review. Japanese. PubMed PMID: 16523968.
18: Chiba K. FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors. Pharmacol Ther. 2005 Dec;108(3):308-19. Epub 2005 Jun 13. Review. PubMed PMID: 15951022.
19: Kahan BD. FTY720: from bench to bedside. Transplant Proc. 2004 Mar;36(2 Suppl):531S-543S. Review. PubMed PMID: 15041402.
20: Aki FT, Kahan BD. FTY720: A new kid on the block for transplant immunosuppression. Expert Opin Biol Ther. 2003 Jul;3(4):665-81. Review. PubMed PMID: 12831371.
