Specifications
Chemical identification
Synonyms: Alaninamide, Bryamycin , Thiactin
RTECS : XN6300100
Thiostrepton is a broad spectrum polypeptide antibiotic which targets a wide range of gram positive and gram negative bacteria.
Further Information
Thiostrepton is soluble in chloroform, dichloromethane, dioxane, pyridine, glacial acetic acid, DMF. Practically insoluble in water, the lower alcohols, nonpolar organic solvents, diluted aqeous acids or bases. It may be dissolved by methanolic acid or base, but with decomposition. Working solution of 1% in DMSO is unstable and should be freshly prepared and protected from light.
Compound Classification
- Polypeptide antibiotic
- Antimicrobial
Thiostrepton perspectives
Thiostrepton is a naturally-occurring antibacterial agent isolated from the soil microorganisms Streptomyces azureus and Streptomyces laurentii. It was first described in 1955 in "Pagano et al., Antibiot. Ann. 1955-56; 554.
Among other antimicrobial drug preparations, Thiostrepton may be used to treat mycobacterial infection, including treatment of tuberculosis.
[1]
. This patent assumes oral administration of Thiostrepton
Thiostrepton was mentioned as a potential agent for the prevention and treatment of Alzheimer's disease, caused by accumulation of amyloid beta peptides [2]
Thiostrepton is a biotechnological tool for producing recombinant proteins in transformed bacteria.[3]
Thiostrepton acts as an anti-malarial agent, by binding to the 23S ribosomal RNA encoded on the malaria parasite plastid DNA [4]
Thiostrepton has been used in veterinary medicine to treat mastitis caused by gram-negative organisms and dermatologic disorders. It is mainly used in ointments containing neomycin, nystatin, Thiostrepton, and topical steroids.
Thiostrepton is also active against gram-positive bacteria.
Thiostrepton has been used as a cattle feed additive, serving as a growth promoter.[5]
Thiostrepton was reported (in 2008) to exhibit activity against breast cancer cells through targeting the transcription factor forkhead box M1 (FOXM1),[12] also in 2011.[13] It has also been shown to circumvent acquired cisplatin resistance in breast cancer cells under in-vitro conditions
[1]
United States Patent Application 20040254100 A1; Filed: 04/05/2004 · Published: 12/16/2004
Vermeulen Mary W, Wu Jiayi, https://www.freepatentsonline.com/y2004/0254100.html
[2]
Weiss et al. Cancer Research (1974), Vol. 34, pages 581-587. Reddy et al. Brain Research Reviews (2005), Vol. 49, pages 618-632
[3]
United States Patent 7709624 B2 · Filed: 04/19/2004 · Published: 05/04/2010; Nakashima et all., https://www.freepatentsonline.com/7709624.html
[4]
United States Patent 6268160, Barbara Clough et al, 2001; https://www.freepatentsonline.com/6268160.html
- Thiostrepton is used as a reagent for both positive and negative selection of genes involved in nucleotide metabolism. Thiostrepton is highly active against gram-positive bacteria. In its crude form, Thiostrepton is used in veterinary medicine, in mastitis caused by gram-negative organisms and in dermatologic disorders. inhibits bacterial protein synthesis. Inhibits mRNA-tRNA translocation by GTPase elongation factor G (EF-G), EF-TU(GTP)-catalyzed aa-tRNA delivery and the activity of initiation factor 2 (IF-2).
As an anti-tumor agent, Thiostrepton induces cell cycle arrest and apoptosis in breast cancer cells via downregulation of FOXM1 expression. Thiostrepton is a FoxM1 specific inhibitor.
More publications
Inhibition of Sonic Hedgehog Signaling Pathway by Thiazole Antibiotic Thiostrepton Attenuates the CD44+/CD24-Stem-Like Population and Sphere-Forming Capacity in Triple-Negative Breast Cancer.
Yang N, Zhou TC, Lei XX, WangC, Yan M, Wang ZF, Liu W, Wang J, Ming KH, Wang BC, Xu BL, Liu Q.
ACS Chem Biol. 2016 Oct 21;11(10):2673-2678.
Identification of Thiostrepton as a Novel Inhibitor for Psoriasis-like Inflammation Induced by TLR7–9
Chao-Yang Lai, Da-Wei Yeh, Chih-Hao Lu, Yi-Ling Liu, Li-Rung Huang, Cheng-Yuan Kao, Huan-Yuan Chen, Chi-Ying F. Huang, Chung-Hsing Chang, Yunping Luo, Rong Xiang and Tsung-Hsien Chuang
The Journal of Immunology October 15, 2015; Volume 195,Issue 8
Molecular mechanism of Forkhead box M1 inhibition by thiostrepton in breast cancer cells
Mesayamas Kongsema, Sudtirak Wongkhieo, Mattaka Khongkow, Eric W.-F. Lam, Phansiri Boonnoy, Wanwipa Vongsangnak, Jirasak Wong-Ekkabut
Oncol Rep. 2019 Sep; 42(3): 953–962. Published online 2019 Jul 8. DOI: 10.3892/or.2019.7225; PMCID: PMC6667886
Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells
S-Y Ju, C-YF Huang, W-C Huang, Y Su
Cell Death Dis. 2015 Jul; 6(7): e1801. Published online 2015 Jul 2. DOI: 10.1038/cddis.2015.155 PMCID: PMC4650716
The dual inhibitory effect of thiostrepton on FoxM1 and EWS/FLI1 provides a novel therapeutic option for Ewing’s sarcoma
ANIRUDDHA SENGUPTA, MAHBUBUR RAHMAN, SILVIA MATEO-LOZANO, OSCAR M. TIRADO, VICENTE NOTARIO
Int J Oncol. 2013 Sep; 43(3): 803–812. Published online 2013 Jul 12. DOI: 10.3892/ijo.2013.2016 PMCID: PMC3787886
Thiostrepton interacts covalently with Rpt subunits of the 19S proteasome and proteasome substrates
Cristinel Sandu, Nagaranjan Chandramouli, Joseph Fraser Glickman, Henrik Molina, Chueh-Ling Kuo, Nikolay Kukushkin, Alfred L Goldberg, Hermann Steller
J Cell Mol Med. 2015 Sep; 19(9): 2181–2192. Published online 2015 May 30. DOI: 10.1111/jcmm.12602 PMCID: PMC4568923
Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells
S-Y Ju, C-YF Huang, W-C Huang & Y Su
Cell Death & Disease volume 6, pagee1801 (2015)