IUPAC/Chemical Name
(2Z,4R,5S,6E)-3,5-dimethoxy-4-methyl-7-[2-[2-[(2S,3E,5E)-7-methylocta-3,5-dien-2-yl]-1,3-thiazol-4-yl]-1,3-thiazol-4-yl]hepta-2,6-dienamide
InChi Key
XKTFQMCPGMTBMD-ZDBABOMLSA-N
InChi Code
InChI=1S/C25H33N3O3S2/c1-16(2)9-7-8-10-17(3)24-28-20(15-33-24)25-27-19(14-32-25)11-12-21(30-5)18(4)22(31-6)13-23(26)29/h7-18,21H,1-6H3,(H2,26,29)/b9-7+,10-8+,12-11+,22-13-/t17-,18+,21-/m0/s1
SMILES Code
O=C(N)/C=C(OC)/[C@H](C)[C@@H](OC)/C=C/C1=CSC(C2=CSC([C@H](/C=C/C=C/C(C)C)C)=N2)=N1
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
>3 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:
Myxothiazol, an antifungal antibiotic, is a mitochondrial electron transport chain complex III (bc1 complex) inhibitor.
In vitro activity:
Myxothiazol, a new antibiotic from the myxobacterium Myxococcus fulvus, inhibited the growth of many yeasts and fungi at concentrations between 0.01 and 3 micrograms/ml. It was generally inactive against bacteria. The inhibitory effect was cytostatic.
Reference: Antimicrob Agents Chemother. 1981 Apr;19(4):504-7. https://pubmed.ncbi.nlm.nih.gov/7247372/
In vivo activity:
This study developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. This study administered myxothiazol intraperitoneally at a dose of 0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice.
Reference: Biochem Biophys Res Commun. 2014 Apr 18;446(4):1079-84. https://pubmed.ncbi.nlm.nih.gov/24661880/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
487.68
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. von Jagow G, Ljungdahl PO, Graf P, Ohnishi T, Trumpower BL. An inhibitor of mitochondrial respiration which binds to cytochrome b and displaces quinone from the iron-sulfur protein of the cytochrome bc1 complex. J Biol Chem. 1984 May 25;259(10):6318-26. PMID: 6327677.
2. Thierbach G, Reichenbach H. Myxothiazol, a new antibiotic interfering with respiration. Antimicrob Agents Chemother. 1981 Apr;19(4):504-7. doi: 10.1128/AAC.19.4.504. PMID: 7247372; PMCID: PMC181466.
3. Davoudi M, Kallijärvi J, Marjavaara S, Kotarsky H, Hansson E, Levéen P, Fellman V. A mouse model of mitochondrial complex III dysfunction induced by myxothiazol. Biochem Biophys Res Commun. 2014 Apr 18;446(4):1079-84. doi: 10.1016/j.bbrc.2014.03.058. Epub 2014 Mar 21. PMID: 24661880.
In vitro protocol:
1. von Jagow G, Ljungdahl PO, Graf P, Ohnishi T, Trumpower BL. An inhibitor of mitochondrial respiration which binds to cytochrome b and displaces quinone from the iron-sulfur protein of the cytochrome bc1 complex. J Biol Chem. 1984 May 25;259(10):6318-26. PMID: 6327677.
2. Thierbach G, Reichenbach H. Myxothiazol, a new antibiotic interfering with respiration. Antimicrob Agents Chemother. 1981 Apr;19(4):504-7. doi: 10.1128/AAC.19.4.504. PMID: 7247372; PMCID: PMC181466.
In vivo protocol:
1. Davoudi M, Kallijärvi J, Marjavaara S, Kotarsky H, Hansson E, Levéen P, Fellman V. A mouse model of mitochondrial complex III dysfunction induced by myxothiazol. Biochem Biophys Res Commun. 2014 Apr 18;446(4):1079-84. doi: 10.1016/j.bbrc.2014.03.058. Epub 2014 Mar 21. PMID: 24661880.
1: Starkov AA, Fiskum G. Myxothiazol induces H(2)O(2) production from mitochondrial respiratory chain. Biochem Biophys Res Commun. 2001 Mar 2;281(3):645-50. PubMed PMID: 11237706.
2: Young TA, Cunningham CC, Bailey SM. Reactive oxygen species production by the mitochondrial respiratory chain in isolated rat hepatocytes and liver mitochondria: studies using myxothiazol. Arch Biochem Biophys. 2002 Sep 1;405(1):65-72. PubMed PMID: 12176058.
3: Weinig S, Mahmud T, Müller R. Markerless mutations in the myxothiazol biosynthetic gene cluster: a delicate megasynthetase with a superfluous nonribosomal peptide synthetase domain. Chem Biol. 2003 Oct;10(10):953-60. PubMed PMID: 14583261.
4: Lai B, Zhang L, Dong LY, Zhu YH, Sun FY, Zheng P. Impact of inhibition of Qo site of mitochondrial complex III with myxothiazol on persistent sodium currents via superoxide and protein kinase C in rat hippocampal CA1 cells. Neurobiol Dis. 2006 Jan;21(1):206-16. Epub 2005 Aug 2. PubMed PMID: 16081299.
5: Perlova O, Fu J, Kuhlmann S, Krug D, Stewart AF, Zhang Y, Müller R. Reconstitution of the myxothiazol biosynthetic gene cluster by Red/ET recombination and heterologous expression in Myxococcus xanthus. Appl Environ Microbiol. 2006 Dec;72(12):7485-94. Epub 2006 Sep 22. PubMed PMID: 16997979; PubMed Central PMCID: PMC1694261.
6: Midzak AS, Liu J, Zirkin BR, Chen H. Effect of myxothiazol on Leydig cell steroidogenesis: inhibition of luteinizing hormone-mediated testosterone synthesis but stimulation of basal steroidogenesis. Endocrinology. 2007 Jun;148(6):2583-90. Epub 2007 Mar 1. PubMed PMID: 17332065.
7: Sandmann A, Frank B, Müller R. A transposon-based strategy to scale up myxothiazol production in myxobacterial cell factories. J Biotechnol. 2008 Jun 30;135(3):255-61. doi: 10.1016/j.jbiotec.2008.05.001. Epub 2008 May 13. PubMed PMID: 18555551.
8: Davoudi M, Kallijärvi J, Marjavaara S, Kotarsky H, Hansson E, Levéen P, Fellman V. A mouse model of mitochondrial complex III dysfunction induced by myxothiazol. Biochem Biophys Res Commun. 2014 Apr 18;446(4):1079-84. doi: 10.1016/j.bbrc.2014.03.058. Epub 2014 Mar 21. PubMed PMID: 24661880.
