(-)-Neplanocin A
目录号 : GC45251
Irreversible SAH hydrolase inhibitor
Cas No.:72877-50-0
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
S-Adenosylhomocysteine (SAH) hydrolase catalyzes the reversible hydrolysis of SAH to adenosine and homocysteine. The inhibition of SAH hydrolase causes the intracellular accumulation of SAH, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase. (-)-Neplanocin A potently and irreversibly inactivates SAH hydrolase (Ki = 8.39 nM). It has antitumor activity against mouse leukemia L1210 cells and broad-spectrum antiviral activity. Neplanocin A is more potent against vesicular stomatitis than the reversible SAH hydrolase inhibitor 3-deazaneplanocin (ID50 = 0.07 and 0.3 μg/ml, respectively).
| Cas No. | 72877-50-0 | SDF | |
| Canonical SMILES | OCC1=C[C@@H](N2C=NC3=C2N=CN=C3N)[C@H](O)[C@@H]1O | ||
| 分子式 | C11H13N5O3 | 分子量 | 263.3 |
| 溶解度 | DMF: 0.2 mg/ml,DMSO: 3 mg/ml,PBS (pH 7.2): 0.3 mg/ml | 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 | 3.7979 mL | 18.9897 mL | 37.9795 mL |
| 5 mM | 0.7596 mL | 3.7979 mL | 7.5959 mL |
| 10 mM | 0.3798 mL | 1.899 mL | 3.7979 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。
Differences in the metabolism and metabolic effects of the carbocyclic adenosine analogs, neplanocin A and aristeromycin
Mol Pharmacol 1986 Apr;29(4):383-90.PMID:3702857doi
Neplanocin A and aristeromycin are carbocyclic adenosine analogs that differ only in that neplanocin A contains a double bond in the carbocyclic ring, whereas this ring in aristeromycin is saturated. We have compared the metabolism and some of the metabolic effects of neplanocin A and synthetic (+/-)-aristeromycin (C-Ado) in murine leukemia L1210 cells in culture. C-Ado, as shown earlier, was not only converted to its own phosphates but also was metabolized to phosphates of carbocyclic guanosine. Both rapidly proliferating and slowly proliferating or resting cells phosphorylated C-Ado, but C-Ado was not converted to phosphates of carbocyclic guanosine in detectable amounts in cells whose growth had reached a plateau. When the metabolism of neplanocin and C-Ado was examined in the same experiment, both analogs were converted to the triphosphate analogs of ATP; no conversion of neplanocin A to the corresponding carbocyclic analogs of guanine nucleotides was detected, whereas C-Ado was converted to the carbocyclic analog of GTP in amounts that approximated the GTP pool. This difference in metabolism was associated with a marked difference in effects of the two analogs on the utilization of hypoxanthine and guanine which was inhibited by C-Ado but not by neplanocin. The failure of neplanocin A to be converted to analogs of guanine nucleotides apparently is the result of poor capacity of its monophosphate to serve as a substrate for AMP deaminase; the Vmax for deamination of neplanocin-5'-monophosphate by this enzyme was only 5% of that for C-Ado monophosphate. In contrast, neplanocin A was a better substrate than C-Ado for adenosine deaminase.
The design and synthesis of a new anticancer drug based on a natural product lead compound: from neplanocin A to cyclopentenyl cytosine (CPE-C)
Stem Cells 1994 Jan;12(1):7-12.PMID:8142923DOI:10.1002/stem.5530120105.
In 1979, an unusual, carbocyclic nucleoside was discovered in a Japanese fermentation broth and designated neplanocin A. This compound is an analog of adenosine possessing a cyclopentene-containing "sugar" glycon. Although neplanocin A was biologically active, it was quite toxic. It therefore became a lead compound for analog synthesis in an attempt to maximize antitumor and antiviral activity while minimizing toxicity. First, a total synthesis of naturally occurring (-)-Neplanocin A was accomplished using a new, versatile cyclopentenone carbocyclic "sugar" intermediate. This intermediate was then used to synthesize some 20 purine and pyrimidine analogs of neplanocin A which were evaluated for their antitumor and antiviral properties. Among the purine analogs, 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase, was found to have excellent antiviral activity both in vitro and in vivo. Cyclopentenyl cytosine (CPE-C) was found to be the most biologically active compound among the carbocyclic pyrimidine nucleosides. In addition to activity against over 20 viruses, this compound had excellent preclinical antitumor activity against both murine leukemias and human tumor xenografts. CPE-C is currently under clinical evaluation as an anticancer drug.
New neplanocin analogues. VIII. Synthesis and biological activity of 6'-C-ethyl, -ethenyl, and -ethynyl derivatives of neplanocin A
Chem Pharm Bull (Tokyo) 1997 Jul;45(7):1163-8.PMID:9246750DOI:10.1248/cpb.45.1163.
This report describes the synthesis and antiviral effects of (6'R)-6'-C-ethynyl, -ethenyl, and -ethyl derivatives of neplanocin A (7a, 8a, and 9a, respectively) and the corresponding 6'S-diastereomers (7b, 8b, and 9b, respectively), as examples of 6'-C-substituted analogues of neplanocin A. Grignard reaction of the 6'-formyl derivative 4, which was readily prepared from neplanocin A, with ethynylmagnesium bromide gave a diastereomeric mixture of the corresponding 1,2-addition products 5a and 5b. After removal of the protecting groups, (6'R)- and (6'S)-6'-C-ethynylneplanocin A's (7a, 7b) were separated. The corresponding ethenyl derivatives 8a and 8b and ethyl derivatives 9a and 9b were prepared by catalytic hydrogenation of 7a and 7b, respectively. As compared to neplanocin A, the new neplanocin A derivatives were much weaker inhibitors of S-adenosyl-L-homocysteine hydrolase, the R-diastereomers being more inhibitory than the S-diastereomers. The decreasing order of activity was 7a > 8a > 7b > 9a > 8b > 9b. The cytotoxicity (for CEM cells) followed exactly the same order. Of these compounds, (6'R)-6'-C-ethynylneplanocin A (7a, RENPA) showed an antiviral activity spectrum that was comparable to, and an antiviral specificity that was higher than, that of neplanocin A. RENPA was particularly active against those viruses (i.e. vaccinia virus, vesicular stomatitis virus) that are known to be highly sensitive to AdoHcy hydrolase inhibitors.