6-Thioinosine
(Synonyms: 6-疏基嘌呤核苷,6TI; 6-Mercaptopurine riboside) 目录号 : GC35171
6-?Thioinosine (6TI) 是一种嘌呤抗代谢物，为抗脂肪形成剂，能够降低 PPAR γ 和 C/EBPα 及其目标基因 LPL，CD36，aP2 和 LXRα 的 mRNA 水平。
Cas No.:574-25-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
6-?Thioinosine (6TI) is a purine antimetabolite, acts as an anti-adipogenesis agent, downregulates mRNA levels of PPAR γ and C/EBPα, as well as PPAR γ target protein such as LPL, CD36, aP2, and LXRα[1][2].
[1]. Lee J, et al. Anti-adipogenesis by 6-thioinosine is mediated by downregulation of PPAR gamma through JNK-dependent upregulation of iNOS. Cell Mol Life Sci. 2010 Feb;67(3):467-81. [2]. Neubert D, et al. Interference of 6-mercaptopurine riboside, 6-methylmercaptopurine riboside and azathioprine with the morphogenetic differentiation of mouse extremities in vivo and in organ culture. Naunyn Schmiedebergs Arch Pharmacol. 1977 Jun;298(2):93-105.
| Cas No. | 574-25-4 | SDF | |
| 别名 | 6-疏基嘌呤核苷,6TI; 6-Mercaptopurine riboside | ||
| Canonical SMILES | S=C1NC=NC2=C1N=CN2C3[C@@H]([C@@H]([C@@H](CO)O3)O)O | ||
| 分子式 | C10H12N4O4S | 分子量 | 284.29 |
| 溶解度 | DMSO: 50 mg/mL (175.88 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 | 3.5175 mL | 17.5877 mL | 35.1753 mL |
| 5 mM | 0.7035 mL | 3.5175 mL | 7.0351 mL |
| 10 mM | 0.3518 mL | 1.7588 mL | 3.5175 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。
Anti-adipogenesis by 6-Thioinosine is mediated by downregulation of PPAR gamma through JNK-dependent upregulation of iNOS
Cell Mol Life Sci 2010 Feb;67(3):467-81.PMID:19941061DOI:10.1007/s00018-009-0196-y.
Adipocyte dysfunction is associated with the development of obesity. This study shows that 6-Thioinosine inhibits adipocyte differentiation. The mRNA levels of PPAR gamma and C/EBPalpha, but not C/EBPbeta and delta, were reduced by 6-Thioinosine. Moreover, the mRNA levels of PPAR gamma target genes (LPL, CD36, aP2, and LXRalpha) were down-regulated by 6-Thioinosine. We also demonstrated that 6-Thioinosine inhibits the transactivation activity and the mRNA level of PPAR gamma. Additionally, attempts to elucidate a possible mechanism underlying the 6-thioinosine-mediated effects revealed that 6-Thioinosine induced iNOS gene expression without impacting eNOS expression, and that this was mediated through activation of AP-1, especially, JNK. In addition, 6-Thioinosine was found to operate upstream of MEKK-1 in JNK activation signaling. Taken together, these findings suggest that the inhibition of adipocyte differentiation by 6-Thioinosine occurs primarily through the reduced expression of PPAR gamma, which is mediated by upregulation of iNOS via the activation of JNK.
Synthesis of 4-thiouridine, 6-Thioinosine, and 6-thioguanosine 3',5'-O-bisphosphates as donor molecules for RNA ligation and their application to the synthesis of photoactivatable TMG-capped U1 snRNA fragments
J Org Chem 2000 Aug 25;65(17):5104-13.PMID:10993333DOI:10.1021/jo991432z.
4-Thiouridine, 6-thioguanosine, and 6-Thioinosine 3',5'-bisphosphates (9, 20, and 28) were synthesized in good yields by considerably improved methods. In the former two compounds, uridine and 2-N-phenylacetylguanosine were converted via transient O-trimethylsilylation to the corresponding 4- and 6-O-benzenesulfonyl intermediates (2 and 13), which, in turn, were allowed to react with 2-cyanoethanethiol in the presence of N-methylpyrrolidine to give 4-thiouridine (3) and 2-N-phenylacetyl-6-thioguanosine derivatives (14), respectively. In situ dimethoxytritylation of these thionucleoside derivatives gave the 5'-masked products 4 and 15 in high overall yields from 1 and 11. 6-S-(2-Cyanoethyl)-5'-O-(4,4'-dimethoxytrityl)-6-thioinosine (23) was synthesized via substitution of the 5'-O-tritylated 6-chloropurine riboside derivative 22 with 2-cyanoethanethiol. These S-(2-cyanoethyl)thionucleosides were converted to the 2'-O-(tert-butyldimethylsilyl)ribonucleoside 3'-phosphoramidite derivatives 7, 18, and 26 or 3',5'-bisphosphate derivatives 8, 19, and 27. Treatment of 8, 19, and 27 with DBU gave thionucleoside 3',5'-bisphosphate derivatives 9, 20, and 28, which were found to be substrates of T4 RNA ligase. These thionucleoside 3',5'-bisphosphates were examined as donors for ligation with m3(2,2,7) G5'pppAmUmA, i.e., the 5'-terminal tetranucleotide fragment of U1 snRNA, The 4-thiouridine 3',5'-bisphosphate derivative 9 was found to serve as the most active substrate of T4 RNA ligase with a reaction efficiency of 96%.
2'-O-Acyl-6-thioinosine cyclic 3',5'-phosphates as prodrugs of thioinosinic acid
J Med Chem 1979 Jul;22(7):811-5.PMID:221658DOI:10.1021/jm00193a012.
A series of 2'-O-acyl derivatives of 6-Thioinosine cyclic 3',5'-phosphate (6-HS-cRMP) were prepared and examined for their cytotoxic effects on S49 mouse lymphoma cells which were deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Cytotoxicity increased with the lipophilicity of the acyl group to a lowest EC50 of 65 micrometer for the 2'-O-palmityl derivative. Addition of a mutation in the gene for cAMP-dependent protein kinase to the HGPRTase-deficient cell line confers resistance to 2'-O-butyryl-cAMP but not to 2'-O-butyryl-6-HS-cRMP, indicating that the latter does not exert its toxic effect via activation of protein kinase. The time course of cell kill by 2'-O-palmityl-6-HS-cRMP resembled that of 6-mercaptopurine and not that of cyclic AMP in these cells. The data suggest that the intact cyclic nucleotides are penetrating the cells and being converted, by phosphodiesterase action and deacylation, to the first toxic metabolite of 6-mercaptopurine, thioinosinic acid.
INHIBITION BY 6-MERCAPTOPURINE OF PURINE PHOSPHORIBOSYLTRANSFERASES FROM EHRLICH ASCITES-TUMOUR CELLS THAT ARE RESISTANT TO THE DRUG
Biochem J 1965 Jan;94(1):71-4.PMID:14342251DOI:10.1042/bj0940071.
1. A strain of Ehrlich ascites-tumour cells that showed little inhibition of growth in the presence of 6-mercaptopurine accumulated less than 5% as much 6-Thioinosine 5'-phosphate in vivo, in the presence of 6-mercaptopurine, as did the sensitive strain from which it was derived. 2. Specific activities of the phosphoribosyltransferases that convert adenine, guanine, hypoxanthine and 6-mercaptopurine into AMP, GMP, IMP and 6-Thioinosine 5'-phosphate were similar in extracts of the resistant and the sensitive cells. 3. As found previously with sensitive cells, 6-mercaptopurine is a competitive inhibitor of guanine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase from the resistant cells and does not inhibit the adenine phosphoribosyltransferase from these cells. Michaelis constants and inhibitor constants of the purine phosphoribosyltransferases from resistant cells did not differ significantly from those measured with the corresponding enzymes from sensitive cells. 4. Resistance to 6-mercaptopurine in this case is probably not due to qualitative or quantitative changes in these transferases.
Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites
Curr Pharm Des 2003;9(31):2627-42.PMID:14529546DOI:10.2174/1381612033453677.
6-Mercaptopurine (6MP) and 6-thioguanine (6TG) are analogs of the natural purines: hypoxanthine and guanine. Both mercaptopurine and thioguanine are substrates for hypoxanthine-guanine phosphoribosyltransferase and are converted into the ribonucleotides 6-thioguanosine monophosphate (6-thioGMP) and 6-Thioinosine monophosphate (T-IMP) respectively. The accumulation of these monophosphates inhibits several vital metabolic reactions. Today, these thiopurine bases remain valuable agents for the induction and maintenance of remissions in patients with myelocytic and acute lymphocytic leukemia. Despite their proved clinical importance, 6MP and 6TG have certain therapeutic disadvantages, which have continued to stimulate the search for purine derivatives enhancing therapeutic efficacy. Considerable efforts have been made to prepare other novel mercaptopurine and thioguanine analogs and their nucleosides to improve the antitumor efficacy. The effectiveness of these thiopurines against certain tumor cell lines suggested that some of these mercaptopurine analogs and their nucleosides would be worthy of consideration in order to determine whether they exert a more selective effect against neoplastic cells than against normal cells or they might be useful in patients whose disease has become resistant to 6MP or 6TG. This review will focus on mercaptopurine analogs and their nucleosides as antimetabolite agents.