Thiolutin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-01722 |
| CAS | 87-11-6 |
| Molecular Weight | 228.29 |
| Molecular Formula | C8H8N2O2S2 |
| Purity | >98% |
Online Inquiry
Description
Thiolutin is a sulfur-containing antibiotic from Streptomyces albus and Streptomyces pimprina that inhibits RNA synthesis directed by all three yeast RNA polymerase.
Specification
| Synonyms | Acetopyrrothin; Acetopyrrothine |
| Storage | -20 °C |
| IUPAC Name | N-(4-methyl-5-oxodithiolo[4,3-b]pyrrol-6-yl)acetamide |
| Canonical SMILES | CC(=O)NC1=C2C(=CSS2)N(C1=O)C |
| InChI | InChI=1S/C8H8N2O2S2/c1-4(11)9-6-7-5(3-13-14-7)10(2)8(6)12/h3H,1-2H3,(H,9,11) |
| InChI Key | MHMRAFONCSQAIA-UHFFFAOYSA-N |
| Source | Streptomyces luteosporeus |
Properties
| Appearance | Yellow Needle Crystal |
| Application | Inhibitor of DNA-primed RNA polimerase and DNA polimerase. Apoptosis inducer. Antineoplastic drug |
| Boiling Point | 478.6±45.0 °C at 760 mmHg |
| Melting Point | 273-276°C |
| Density | 1.6±0.1 g/cm3 |
| Solubility | Soluble in Methanol, Chloroform |
Reference Reading
1. Pharmacological targeting of NLRP3 deubiquitination for treatment of NLRP3-associated inflammatory diseases
Ya-Ting Li, Miao Yu, Guang-Ming Ren, Xian Liu, Rong-Hua Yin, Chang-Hui Ge, Jie Zhang, Yi-Qun Zhan, Kai Liu, Xiao-Ming Yang, Xuan-Yi Zhang, Shou-Song Tao, Chang-Yan Li, Gui-Fang Dou, Wen Zhang, Jian Li, Bo-Xue Tian, Hui Chen, Ting Wang, Xiao-Chun Zhang, Yu Wang, Yang Xiao, Wen-Bing Ma Sci Immunol . 2021 Apr 30;6(58):eabe2933. doi: 10.1126/sciimmunol.abe2933.
Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate-induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)-mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.
2. The PSMD14 inhibitor Thiolutin as a novel therapeutic approach for esophageal squamous cell carcinoma through facilitating SNAIL degradation
Yansheng Wu, Mengqian Zhou, Linqi Li, Yue Wu, Dandan Liu, Kai Yue, Xingchen Li, Xudong Wang, Yuansheng Duan, Peng Chen, Beibei Ye, Xiaofeng Yao, Qingchuan Lai, Shengchi Zhang, Hong Li, Chao Jing Theranostics . 2021 Apr 3;11(12):5847-5862. doi: 10.7150/thno.46109.
Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC.Methods:Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by usingin vitroandin vivoexperiments. Immunoprecipitation andin vivoubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14.Results:Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results ofin vitroandin vivoassays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer.Conclusion:Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.
3. Thiolutin resistant mutants of Escherichia coli are they RNA chain initiation mutants?
R Jayaraman, N Sivasubramanian Mol Gen Genet . 1976 Apr 23;145(1):89-96. doi: 10.1007/BF00331562.
Four mutants of Escherichia coli KL16 resistant to the antibiotic Thiolutin have been isolated. This drug was earlier reported to be an inhibitor of RNA chain elongation. The first mutant, TLrI, is resistant only in rich or partially rich media: it can, however, grow in minimal medium containing the drug with a very long doubling time. The other mutants TLrII, TLrIIIa and TLrIIIb are resistant in rich as well as minimal media. beta-galactosidase could not be induced in TLrI and TLrII in the presence of thiolutin whereas the enzyme is constitutively synthesised in TLrIIIa and TLrIIIb irrespective of the drug. The mutants do not support the development of phage T4 in presence of the drug, if the drug is added along with the phage, but "escape" the inhibition if phage development is allowed to proceed for some time before the addition of the drug. The time of this escape is characteristic of the mutant. Even in a sensitive strain, T7 growth escapes inhibition very soon after infection, around the time the phage-specific RNA polymerase is synthesized. In the parent strain the kinetics of inhibition of beta-galactosidase induction resembles more the inhibition caused by rifampicin than by streptolydigin. It is proposed that thiolutin could be an inhibitor of RNA chain initiation and resistance might be due to mutation in the subunit(s)/factor(s) involved in initiation.
Recommended Products
| BBF-03753 | Baicalin | Inquiry |
| BBF-03755 | Actinomycin D | Inquiry |
| BBF-00677 | 3-Amino-3-deoxy-D-glucose | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-01825 | Loganin | Inquiry |
| BBF-01693 | Doxorubicin EP Impurity A (Daunorubicin) | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
