Sinefungin
(Synonyms: 西奈芬净,Adenosyl-Ornithine; A-9145; Antibiotic 32232RP) 目录号 : GC34784
Sinefungin是病毒mRNA(鸟嘌呤-7-)-甲基转移酶、mRNA(核苷-2'-)-甲基转移酶和病毒增殖的有效抑制剂。Sinefungin是一种SET7/9抑制剂，通过抑制H3K4甲基化来改善肾纤维化。
Cas No.:58944-73-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sinefungin is a potent inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication[1]. Sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4 methylation [2].
[1]. Pugh CS, et al. Sinefungin, a potent inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication. J Biol Chem. 1978 Jun 25;253(12):4075-7. [2]. Sasaki K, et al. Inhibition of SET Domain-Containing Lysine Methyltransferase 7/9 Ameliorates Renal Fibrosis. J Am Soc Nephrol. 2016 Jan;27(1):203-15.
| Cas No. | 58944-73-3 | SDF | |
| 别名 | 西奈芬净,Adenosyl-Ornithine; A-9145; Antibiotic 32232RP | ||
| Canonical SMILES | O[C@H]([C@@H]1O)[C@@H](O[C@@H]1C[C@@H](N)CC[C@H](N)C(O)=O)N2C(N=CN=C3N)=C3N=C2 | ||
| 分子式 | C15H23N7O5 | 分子量 | 381.39 |
| 溶解度 | Water : 100 mg/mL (262.20 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 | 2.622 mL | 13.1099 mL | 26.2199 mL |
| 5 mM | 0.5244 mL | 2.622 mL | 5.244 mL |
| 10 mM | 0.2622 mL | 1.311 mL | 2.622 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。
Carbocyclic Sinefungin
Tetrahedron Lett 2007 Jul 9;48(28):4809-4811.PMID:18612331DOI:10.1016/j.tetlet.2007.05.079.
(3aS,4S,6R,6aR)-Tetrahydro-2,2-dimethyl-6-vinyl-3aH-cyclopenta[d][1,3]-dioxol-4-ol, itself available from ribose, provided a convenient entry point for an 18-step preparation of carbocyclic Sinefungin. This procedure is adaptable to a number of carbocyclic Sinefungin analogs with diversity of heterocyclic base and in the amino acid bearing side chain.
Asymmetric Total Synthesis of C9'- epi-Sinefungin
Org Lett 2020 Jul 17;22(14):5594-5599.PMID:32628491DOI:10.1021/acs.orglett.0c01956.
The natural nucleoside (+)-sinefungin, structurally similar to cofactor S-adenosyl-l-methionine, inhibits various SAM-dependent methyltransferases (MTs). Access to Sinefungin analogues could serve as the basis for the rational design of small molecule methyltransferase inhibitors. We developed a route to the unnatural C9' epimer of Sinefungin that employed a diastereoselective Overman rearrangement to install the key C6' amino stereocenter. The ability for late-stage modification is highlighted, opening an avenue for the discovery of new MT inhibitors.
Sinefungin-PLGA nanoparticles: drug loading, characterization, in vitro drug release and in vivo studies
J Nanosci Nanotechnol 2009 Jan;9(1):150-8.PMID:19441289DOI:10.1166/jnn.2009.j018.
Cryptosporidiosis, the leading cause of endemic and epidemic diarrhoeal disease worldwide is due to Cryptosporidium parvum, a spore-forming protozoan. Anticryptosporidial pharmacological and/or immunological agents were initially tested in immunodeficient models of cryptosporidiosis, and Sinefungin exhibited a significant dose dependent curative and preventive activity. Shedding relapses observed after discontinuation of Sinefungin therapy lead to identify the bile ducts as a protected reservoir that may sustain chronic infection. The MIC50 of the Sinefungin observed in vitro studies is 14.5 microg/ml. It is a hydrophilic drug lowly absorbed when orally administered and nephrotoxic after IV injection. To avoid this toxic effect, Neal's team prepared Sinefungin loaded microspheres and proved that encapsulated Sinefungin was 10 times more effective than free Sinefungin. This optimistic result led us to study the nanoparticles as drug carrier for Sinefungin. In this study, we prepared optimal Sinefungin loaded PLGA nanoparticles. Physico-chemical characterization, in vitro drug release and in vivo studies were assessed. Negative surface-charged (-56.1 mV) Sinefungin loaded PLGA nanoparticles were prepared with a homogenous size of 200 nm. Optimal formulation led to a drug content of 9.18% w/w (4.59 mg) and a drug entrapment of 15.16%. Dilution technique was used to study the release of Sinefungin in vitro. 93.03% of Sinefungin were released from dilution 1:5 to 1:20. This burst effect could probably due to the adsorption of the drug on the surface of the nanoparticles. A second step with a lower release was observed from dilution 1:20 to 1:100 which may correspond to the diffusion out of the drug solution from the nanoparticles into the bulk release medium. Investigations in rats showed that only 1.23 mg of Sinefungin loaded in PLGA nanoparticles led to a decrease of Sinefungin in the urine (0.23 mg vs. 4.27 mg for IV administration of free Sinefungin) and to an increase of Sinefungin concentration in the bile (6.63 microg/ml vs. 3.89 microg/ml for IV administration of free Sinefungin). But the biliary concentration of encapsulated Sinefungin (6.63 microg/ml) is still nearly 2 times lower than the MIC50.
The S-adenosylmethionine analog Sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening
FEBS Lett 2022 Jan;596(1):42-52.PMID:34817067DOI:10.1002/1873-3468.14240.
Mutations in many genes that control the expression, the function, or the stability of telomerase cause telomere biology disorders (TBDs), such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia. Mutations in a subset of the genes associated with TBDs cause reductions of the telomerase RNA moiety hTR, thus limiting telomerase activity. We have recently found that loss of the trimethylguanosine synthase TGS1 increases both hTR abundance and telomerase activity and leads to telomere elongation. Here, we show that treatment with the S-adenosylmethionine analog Sinefungin inhibits TGS1 activity, increases the hTR levels, and promotes telomere lengthening in different cell types. Our results hold promise for restoring telomere length in stem and progenitor cells from TBD patients with reduced hTR levels.
Sinefungin resistance of Saccharomyces cerevisiae arising from Sam3 mutations that inactivate the AdoMet transporter or from increased expression of AdoMet synthase plus mRNA cap guanine-N7 methyltransferase
Nucleic Acids Res 2007;35(20):6895-903.PMID:17932050DOI:10.1093/nar/gkm817.
The S-adenosylmethionine (AdoMet) analog Sinefungin is a natural product antibiotic that inhibits nucleic acid methyltransferases and arrests the growth of unicellular eukarya and eukaryal viruses. The basis for the particular sensitivity of fungi and protozoa to Sinefungin is not known. Here we report the isolation and characterization of spontaneous sinefungin-resistant mutants of the budding yeast Saccharomyces cerevisiae. In all cases, Sinefungin resistance was attributable to a loss-of-function mutation in Sam3, the yeast high-affinity AdoMet transporter. Overexpression of wild-type Sam3 increased the sensitivity of yeast to growth inhibition by Sinefungin. Thus, Sam3 is a tunable determinant of Sinefungin potency. The shared ability of protozoan parasites to import AdoMet might determine Sinefungin's anti-infective spectrum. Insights to the intracellular action of Sinefungin stem from the finding that increased gene dosage of yeast AdoMet synthase plus cap guanine-N7 methyltransferase afforded greater resistance to Sinefungin than either enzyme alone. These results are consistent with the proposal that mRNA cap methylation is a principal target of Sinefungin's bioactivity.