Tiamulin fumarate (Thiamutilin fumarate)
(Synonyms: 延胡索酸泰妙菌素; Thiamutilin fumarate) 目录号 : GC32091
A pleuromutilin antibiotic
Cas No.:55297-96-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tiamulin is a pleuromutilin antibiotic.1 It is active against M. gallisepticum, M. synoviae, M. iowae, M. hyopneumoniae, M. hyosynoviae, M. hyorhinis, M. bovis, and M. agalactiae (MICs = 0.0025-0.25 ?g/ml). Tiamulin is also active against various Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA).2 Tiamulin binds to the peptidyl transferase in the 50S ribosomal subunit to inhibit protein synthesis. Formulations containing tiamulin have been used in the treatment of veterinary enteric diseases and enzootic pneumonia.
1.Hannan, P.C.T., Windsor, G.D., de Jong, A., et al.Comparative susceptibilities of various animal-pathogenic mycoplasmas to fluoroquinolonesAntimicrob. Agents Chemother.41(9)2037-2040(1997) 2.Wilson, D.N.The A-Z of bacterial translation inhibitorsCrit. Rev. Biochem. Mol. Biol.44(6)393-433(2009)
| Cas No. | 55297-96-6 | SDF | |
| 别名 | 延胡索酸泰妙菌素; Thiamutilin fumarate | ||
| Canonical SMILES | O=C(O[C@H]1[C@]([C@H](C)CC2)(C)[C@@](C(CC3)=O)([H])[C@]32[C@@H](C)[C@H](O)[C@](C)(C=C)C1)CSCCN(CC)CC.O=C(O)/C=C/C(O)=O | ||
| 分子式 | C32H51NO8S | 分子量 | 609.81 |
| 溶解度 | DMSO : ≥ 50 mg/mL (81.99 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6399 mL | 8.1993 mL | 16.3986 mL |
| 5 mM | 0.328 mL | 1.6399 mL | 3.2797 mL |
| 10 mM | 0.164 mL | 0.8199 mL | 1.6399 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Tiamulin inhibits TNF-α and alleviates psoriasis-like dermatitis
J Dermatol Sci 2022 Jul;107(1):32-40.PMID:35718680DOI:10.1016/j.jdermsci.2022.05.006.
Background: TNF-α elicits a cascade amplification effect in psoriasis. Macromolecule drugs targeting TNF-α are widely used for the clinical treatment of psoriasis. However, there are currently no effective small-molecule inhibitors that can be used in the clinic. Objective: Novel TNF-α inhibitor was identified via high-throughput screening (HTS) and its anti-inflammatory activity was evaluated. Methods: Two cell death models were established to identify inhibitors of TNF-α through HTS from a library of 3256 compounds. The effect of the inhibitor of TNF-α was tested by HaCaT cells in vitro and IMQ-induced psoriasis-like mouse model in vivo. Results: Tiamulin fumarate (TF) was identified as an effective inhibitor of TNF-α. TF significantly blocked the NF-κB and MAPK signaling pathways in TNF-α-stimulated HaCaT cells. Additionally, systemic and topical administration of TF improved IMQ-induced psoriasis-like dermatitis in the mouse model. Conclusion: Our study established a HTS method to identify TF as an inhibitor of TNF-α. The protective roles of TF in psoriasis-related inflammation reveal the potential therapeutic value of TF for psoriasis.
Pharmacokinetics, bioavailability, and tissue disposal profiles of Tiamulin fumarate in Nile tilapia (Oreochromis niloticus) following oral and intravenous administrations
J Vet Pharmacol Ther 2021 Jul;44(4):590-602.PMID:33675107DOI:10.1111/jvp.12957.
Tiamulin fumarate (TIF) is a pleuromutilin antibiotic and has high activity against animal bacterial pathogens including aquatic bacterial pathogens. However, its pharmacokinetic profiles, tissue distribution characteristics and bioavailability in aquatic animals remain unknown. The objective of this study was to investigate the pharmacokinetics and tissue distribution regularities of TIF in tilapia (Oreochromis niloticus) following a single oral (PO) dose of 20 mg/kg body weight (bw) and a single intravenous (IV) dose of 5 mg/kg bw at 22 ± 1°C, respectively. TIF concentrations in tilapia plasma and tissues were determined using the isotope dilution HPLC-HESI-MS/MS procedure, which was validated according to the guidelines defined by US Food and Drug Administration. TIF was well distributed throughout the body compartments of tilapia judged by the apparent volume of distribution (Vd ) >1 L/kg (6.69 L/kg PO and 1.78 L/kg IV). TIF had a short mean residence time (MRT; 22.82 h PO and 14.61 h IV) and quick total body clearance (CLb ) (0.62 L kg-1 h-1 PO and 0.60 L kg-1 h-1 IV). The total area under the curve (AUCtot ) of plasma were 32.25 μg h-1 ml-1 (PO) and 8.30 μg h-1 ml (IV), respectively, and the oral absolute bioavailability (F%) of TIF was calculated to be approximately 97.1%. For tissue distribution, high concentrations of TIF were found in kidney, and the longest MRT was recorded in bile. The withdrawal time (WT) of TIF in muscle, skin, liver, kidney, gill, and bile was 3.75 (4) and 1.79 (2), 1.77 (2) and 2.06 (3), 6.41 (7) and 1.97 (2), 6.95 (7) and 3.98 (4), 4.92 (5) and 2.36 (3), and 7.06 (8) and 6.16 (7) days after PO and IV administration, respectively. The present investigations indicated that TIF was quickly absorbed, well distributed, rapidly eliminated in tilapia, and it could serve as reference data for establishing use regimen and provide useful information for the further development of TIF in aquaculture.
In Vitro and In Vivo Activity of 14- O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus
Molecules 2021 May 28;26(11):3277.PMID:34071703DOI:10.3390/molecules26113277.
Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed Tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.
Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives
Molecules 2017 Jun 15;22(6):996.PMID:28617344DOI:10.3390/molecules22060996.
A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR), and High Resolution Mass Spectrometer (HRMS). Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus (VRE) in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, 3a, 3b, and 3f, displayed modest antibacterial activities. Compound 3a, the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of Tiamulin fumarate. Moreover, molecular docking studies of 3a and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives.
Antibacterial activity and pharmacokinetic profile of a promising antibacterial agent: 14-O-[(4-Amino-6-hydroxy-pyrimidine-2-yl)thioacetyl] mutilin
Pharmacol Res 2018 Mar;129:424-431.PMID:29133214DOI:10.1016/j.phrs.2017.11.010.
A new pleuromutilin derivative, 14-O-[(4-Amino-6-hydroxy-pyrimidine-2-yl)thioacetyl] mutilin (APTM), has been synthesized and proved most potent antibacterial agent in in vitro assays, suggesting that further development of this compound may lead to a promising antibacterial drug. In this study, we further evaluated the cytotoxicity, antibacterial efficacy and the pharmacokinetic profile of APTM. In BRL 3A cells, 50% of viability was obtained when 363μg/mL of APTM was used, while retapamulin and Tiamulin fumarate needed 49 and 28μg/mL, respectively, to reach this viability. Compared to Tiamulin fumarate, APTM showed higher inhibition efficacy and faster bactericidal activity against S. aureus and lower 50% effective dose (ED50) in mice after a lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA). Docking experiment for APTM showed a similar binding pattern with tiamulin. Furthermore, a simple, accurate and sensitive HPLC method for the determination of APTM in rabbit plasma was developed and successfully applied to pharmacokinetic study, in which the half life (t1/2), clearance rate (Cl) and the area under the plasma concentration-time curve (AUC0→∞) were 3.37h, 0.35L/h/kg and 70.68μg·h/m, respectively.