1393-48-2

Basic information

• Product Name: THIOSTREPTON
• Synonyms: Thiostrepton (200 mg);BryaMycin, Thiactin, AlaninaMide, X 146, A 8506, 6761-31;Thiostrepton, froM StreptoMyces sp.;AlaninaMide,N-[(7R,8S)-2-carboxy-7,8-dihydro-8-hydroxy-4-[(1S)-1-hydroxyethyl]-7-quinolinyl]-L-isoleucyl-L-alanyl-2,3-didehydroalanyl-L-alanyl-2-[(4aR,11S,14Z,18S,21S,28S,32aS)-4a-aMino-21-[(1S,2R)-1,2-dihydroxy-1-Methylpropyl]-14-ethylidene-3,4,4a,9,10,1;a-8506;antibiotic6761-31;antibiotica8506;antibioticx146
• CAS NO: 1393-48-2
• Molecular Formula: C72H85N19O18S5
• Molecular Weight: 1664.89
• EINECS: 215-734-9
• Product Categories: Antibacterial;Antibiotics;Antibiotics A to;Antibiotics by Application;Antibiotics T-ZAntibiotics;Chemical Structure Class;Gene Regulation and Expression;Genetic Marker SelectionAntibiotics;Interferes with Protein SynthesisSpectrum of Activity;L - ZAntibiotics;Mechanism of Action;PeptidesCell Signaling and Neuroscience;Peptide Synthesis/Antibiotics;Amino Acids & Derivatives;Intermediates & Fine Chemicals;Pharmaceuticals;BETAPACE;antibiotic;Inhibitors;Organics;RNA-Protein Translation InhibitorsMore...Close...
• Mol File: 1393-48-2.mol
• Article Data: 0

Chemical Properties

• Melting Point: 248-257°C (dec.)
• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.0824 (rough estimate)
• Refractive Index: 1.6700 (estimate)
• Storage Temp.: −20°C
• Solubility: Soluble in DMSO or chloroform
• PKA: 10.43±0.46(Predicted)
• Water Solubility: 0.24g/L(28 oC)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 week.
• Merck: 13,9440
• CAS DataBase Reference: THIOSTREPTON(CAS DataBase Reference)
• NIST Chemistry Reference: THIOSTREPTON(1393-48-2)
• EPA Substance Registry System: THIOSTREPTON(1393-48-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: XN6300100
• F: 10-21
• Hazardous Substances Data: 1393-48-2(Hazardous Substances Data)

Usage

Description

THIOSTREPTON is a macrocyclic antibiotic that contains thiazoles and other atypical amino acids. It was patented in 1961 and is derived from Streptomyces. THIOSTREPTON acts as a protein synthesis-inhibiting agent by binding to ribosomes, preventing the binding of the EF-G elongation factor and GTP to the 50S ribosomal subunit. It is also an inducer of the tipA gene, which controls bacterial transcription regulators involved in multidrug resistance. THIOSTREPTON is closely related to siomycin, an inhibitor of the oncogenic transcription factor FoxM1. It is a thiazole-containing peptide antibiotic that inhibits the function of elongation factor G (EF-G) and the dissociation of EF-G from the ribosome. The thiostrepton-resistant gene is commonly used as a selective marker for recombinant DNA/plasmid technologies. THIOSTREPTON is also a natural peptide thiazole antibiotic that inhibits FoxM1 in mammalian cells, preventing the expression of FoxM1-regulated genes and inducing apoptosis in human cancer cells. It is an off-white solid.

Uses

1. Used in Pharmaceutical Industry:
THIOSTREPTON is used as an antibiotic for its ability to inhibit bacterial protein synthesis by preventing the binding of EF-G and GTP to the 50S ribosomal subunit.
2. Used in Genetic Engineering:
THIOSTREPTON is used as a selective marker for recombinant DNA/plasmid technologies due to the presence of the thiostrepton-resistant gene.
3. Used in Anticancer Applications:
THIOSTREPTON is used as an anticancer agent, particularly for its ability to inhibit the oncogenic transcription factor FoxM1, preventing the expression of FoxM1-regulated genes and inducing apoptosis in human cancer cells.
4. Used in Research and Development:
THIOSTREPTON is used as a tool in the study of protein synthesis, ribosome function, and the development of new antibiotics and anticancer drugs.
5. Used in Drug Resistance Studies:
THIOSTREPTON is used to investigate the role of the tipA gene and its control over bacterial transcription regulators in multidrug resistance.

Biochem/physiol Actions

Primary TargetEF-G

in vitro

thiostrepton inhibits the transcriptional activity and foxm1 expression, and induces strong apoptosis in human cancer cells of different origin that correlates with suppression of foxm1, including leukemia, neuroblastoma, liver cancer, melanoma and prostate cancer cells. thiostrepton binds foxm1 on the promoter site to inhibit transcriptional activity of foxm1 through the foxm1 autoregulation mechanism [1].

in vivo

thiostrepton suppressed tumor growth in a human breast cancer xenograft model. treatment with developed micelle-thiostrepton nanoparticles decreased xenograft tumor growth induced by the human mda-mb-231 breast and hepg2 liver cancer cell lines. these apoptosis activities in drug-treated tumors were correlated with in vivo suppression of oncogenic foxm1 [1].

References

1) Bowen et al. (2005), Interaction of thiostrepton and elongation factor-G with the ribosomal protein L11-binding domain; J. Biol. Chem., 280 2934 2) Gonzalez et al. (2007), Thiostrepton inhibition of tRNA delivery to the ribosome; RNA, 13 2091 3) Kwok et al. (2008), Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression; Mol. Cancer Ther., 7 2022

InChI:InChI=1/C72H85N19O18S5/c1-14-26(3)47-63(105)78-30(7)57(99)75-28(5)56(98)76-31(8)58(100)91-72-19-18-40(66-85-43(22-111-66)59(101)77-29(6)55(97)74-27(4)54(73)96)81-52(72)42-21-112-67(83-42)49(34(11)109-69(107)41-20-37(32(9)92)36-16-17-39(79-47)51(95)50(36)80-41)89-60(102)44-24-113-68(86-44)53(71(13,108)35(12)94)90-62(104)45-23-110-65(84-45)38(15-2)82-64(106)48(33(10)93)88-61(103)46-25-114-70(72)87-46/h15-17,20-22,24-26,30-35,39,45,47-49,51-53,79,92-95,108H,4-6,14,18-19,23H2,1-3,7-13H3,(H2,73,96)(H,74,97)(H,75,99)(H,76,98)(H,77,101)(H,78,105)(H,82,106)(H,88,103)(H,89,102)(H,90,104)(H,91,100)/b38-15+

Related news

Influence of THIOSTREPTON (cas 1393-48-2) binding on the ribosomal GTPase associated region characterized by molecular dynamics simulation09/09/2019

The thiostrepton antibiotic inhibits bacterial protein synthesis by binding to a cleft formed by the ribosomal protein L11 and 23S’s rRNA helices 43–44 on the 70S ribosome. It was proposed from crystal structures that the ligand restricts L11’s N-terminal movement and thus prevents proper tra...detailed

THIOSTREPTON (cas 1393-48-2) binds to malarial plastid rRNA09/08/2019

Binding of the thiazolyl peptide antibiotic thiostrepton to the GTPase domain of 23S rRNA involves a few crucial nucleotides, notably A1067 (E. coli). Small RNA transcripts were prepared corresponding to the GTPase domain of the plastid 23S rRNA and the two forms of cytosolic 28S rRNAs found in ...detailed

Functional roles in S-adenosyl-l-methionine binding and catalysis for active site residues of the THIOSTREPTON (cas 1393-48-2) resistance methyltransferase09/07/2019

Resistance to the antibiotic thiostrepton, in producing Streptomycetes, is conferred by the S-adenosyl-l-methionine (SAM)-dependent SPOUT methyltransferase Tsr. For this and related enzymes, the roles of active site amino acids have been inadequately described. Herein, we have probed SAM interac...detailed

Synthesis of dehydroalanine fragments as THIOSTREPTON (cas 1393-48-2) side chain mimetics09/06/2019

Syntheses of dehydroalanine derivatives via a solid-support route, starting from selenocystein, and via conventional solution phase chemistry are described along with initial biological testing. The target compounds were designed as mimetics of the dehydroalanine side chain of the macrocyclic an...detailed

Synthetic studies on THIOSTREPTON (cas 1393-48-2) family of peptide antibiotics: synthesis of the dihydroquinoline portion of THIOSTREPTON (cas 1393-48-2), the siomycins, and the thiopeptins09/05/2019

Synthesis of the dihydroquinoline portion of thiostrepton, the siomycins, and the thiopeptins, members of the thiostrepton family of peptide antibiotics, has been achieved featuring the one-pot olefination via the Matsumura–Boekelheide rearrangement “using trifluoromethanesulfonic anhydride an...detailed

THIOSTREPTON (cas 1393-48-2) is an inducer of oxidative and proteotoxic stress that impairs viability of human melanoma cells but not primary melanocytes09/04/2019

Pharmacological induction of oxidative and proteotoxic stress has recently emerged as a promising strategy for chemotherapeutic intervention targeting cancer cells. Guided by a differential phenotypic drug screen for novel lead compounds that selectively induce melanoma cell apoptosis without co...detailed

Discovery and efficient synthesis of a biologically active alkaloid inspired by THIOSTREPTON (cas 1393-48-2) biosynthesis09/03/2019

Thiostrepton, a natural peptide macrocycle, is of great interest due to its structural complexity and numerous biological activities, including anti-bacterial, anti-tumor, and anti-plasmodial activities. The quinaldic acid (QA) moiety-containing side ring (loop 2) was proven to play an important...detailed

Development of co-solvent freeze-drying method for the encapsulation of water-insoluble THIOSTREPTON (cas 1393-48-2) in sterically stabilized micelles09/02/2019

The purpose of this work was to develop a practical and scalable method to encapsulate the hydrophobic antibiotic thiostrepton (TST) in sterically stabilized micelles (SSM). Using the conventional method of thin-film hydration, we encapsulated up to 5 drug molecules per SSM (diameter ∼ 16 nm). ...detailed