Aristeromycin
(Synonyms: 芒雷素) 目录号 : GC35387
Aristeromycin，腺苷类似物，是一种抗生素和有效的S-腺苷同型半胱氨酸水解酶 (AHCY) 抑制剂。
Cas No.:19186-33-5
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
Aristeromycin, an adenosine analog, is an antibiotic and a potent S-adenosylhomocysteine hydrolase (AHCY) inhibitor[1][2]. S-adenosylhomocysteine hydrolase[1]
The IC50 value of Aristeromycin against AHCY is 38.5 nM at 50 μM S-adenosylhomocysteine (SAH) (approximately equal to the Km: 48 μM), but 271 nM at 1000 µM SAH (20× Km). With 60 min of preincubation, the mean IC50 value of Aristeromycin at 50 μM SAH is 12.7 nM[1].Aristeromycin has IC50 values of 3.2 μM for LNCaP-FGC cell growth and 0.88 μM for LNCaP-hr cell growth[1].At least in part, Aristeromycin can regulate oncogenic EZH2 expression by inducing miR-26a[1].
[1]. Uchiyama N, et al. Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a. Eur J Pharmacol. 2017 Oct 5;812:138-146. [2]. Ishikura T, et al. Inhibition of S-adenosylhomocysteine hydrolase by purine nucleoside analogues. Nucleic Acids Symp Ser. 1983;(12):119-22.
| Cas No. | 19186-33-5 | SDF | |
| 别名 | 芒雷素 | ||
| Canonical SMILES | O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N2C3=NC=NC(N)=C3N=C2 | ||
| 分子式 | C11H15N5O3 | 分子量 | 265.27 |
| 溶解度 | DMSO : 50 mg/mL (188.49 mM; ultrasonic and warming and heat to 60°C) | 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 | 3.7697 mL | 18.8487 mL | 37.6974 mL |
| 5 mM | 0.7539 mL | 3.7697 mL | 7.5395 mL |
| 10 mM | 0.377 mL | 1.8849 mL | 3.7697 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。
Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a
Eur J Pharmacol 2017 Oct 5;812:138-146.PMID:28705714DOI:10.1016/j.ejphar.2017.07.023.
Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocysteine. DZNeP and Aristeromycin showed high inhibitory activity against AHCY. Treatment of the prostate cancer cells with DZNeP led to SAH accumulation and decreased levels of homocysteine and histone H3K27 methylation. SAH accumulation and cell growth inhibition were confirmed after siRNA-mediated AHCY knockdown. To further understand why AHCY inhibitors decreased prostate cancer cell growth, we performed microRNA expression profiling with LNCaP-hr cells. Mir-26a, which is involved in regulation of EZH2 expression, was upregulated in Aristeromycin-treated LNCaP-hr cells. A reporter assay established with the EZH2 3'-UTR confirmed that transfection of microRNA precursor molecules for miR-26a decreased the EZH2 3'-UTR luciferase activity. Meanwhile, an antisense microRNA inhibitor for miR-26a recovered the luciferase activity. The present findings suggest, at least in part, that miR-26a induced by an AHCY inhibitor can regulate oncogenic EZH2 expression, and could thus be an important mechanism of action for AHCY inhibitors in the treatment of prostate cancer.
Diastereoselective Diboration of Cyclic Alkenes: Application to the Synthesis of Aristeromycin
Org Lett 2021 Apr 16;23(8):2863-2867.PMID:33792325DOI:10.1021/acs.orglett.1c00353.
The Pt-catalyzed diboration of cyclic alkenes is extended to unsaturated heterocycles and bicyclic compounds and can be accomplished in a diastereoselective fashion. The optimal procedures, substrate scope, and diastereoselectivity were investigated, and examples employing both homogeneous and heterogeneous catalysis were examined. Lastly, application to the construction of the nucleoside analog (±)-aristeromycin was conducted.
Cyclic Aristeromycin diphosphate ribose: a potent and poorly hydrolysable Ca(2+)-mobilising mimic of cyclic adenosine diphosphate ribose
FEBS Lett 1996 Feb 5;379(3):227-30.PMID:8603694DOI:10.1016/0014-5793(95)01515-9.
Cyclic Aristeromycin diphosphate ribose, a carbocyclic analogue of cyclic adenosine diphosphate ribose, was synthesised using a chemo-enzymatic route involving activation of Aristeromycin 5'-phosphate by diphenyl phosphochloridate. The calcium-releasing properties of this novel analogue were investigated in sea urchin egg homogenates. While cyclic Aristeromycin diphosphate ribose has a calcium release profile similar to that of cyclic adenosine diphosphate ribose (EC50 values are 80 nM and 30 nM, respectively), it is degraded significantly more slowly (t1/2 values are 170 min and 15 min, respectively) and may, therefore, be a useful tool to investigate the activities of cyclic adenosine diphosphate ribose.
Stereochemistry in the Reaction of the myo-Inositol Phosphate Synthase Ortholog Ari2 during Aristeromycin Biosynthesis
Biochemistry 2019 Dec 24;58(51):5112-5116.PMID:31825604DOI:10.1021/acs.biochem.9b00981.
The myo-inositol-1-phosphate synthase (MIPS) ortholog Ari2, which is encoded in the Aristeromycin biosynthetic gene cluster, catalyzes the formation of five-membered cyclitol phosphate using d-fructose 6-phosphate (F6P) as a substrate. To understand the stereochemistry during the Ari2 reaction in vivo, we carried out feeding experiments with (6S)-d-[6-2H1]- and (6R)-d-[6-2H1]glucose in the aristeromycin-producing strain Streptomyces citricolor. We observed retention of the 2H atom of (6S)-d-[6-2H1]glucose and no incorporation of the 2H atom from (6R)-d-[6-2H1]glucose in Aristeromycin. This indicates that Ari2 abstracts the pro-R proton at C6 of F6P after oxidation of C5-OH by nicotinamide adenine dinucleotide (NAD+) to generate the enolate intermediate, which then attacks the C2 ketone to form the C-C bond via aldol-type condensation. The reaction of Ari2 with (6S)-d-[6-2H1]- and (6R)-d-[6-2H1]F6P in vitro exhibited identical stereochemistry compared with that observed during the feeding experiments. Furthermore, analysis of the crystal structure of Ari2, including NAD+ as a ligand, revealed the active site of Ari2 to be similar to that of MIPS of Mycobacterium tuberculosis, supporting the similarity of the reaction mechanisms of Ari2 and MIPS.
The 5'-nor Aristeromycin analogues of 5'-deoxy-5'-methylthioadenosine and 5'-deoxy-5'-thiophenyladenosine
Nucleosides Nucleotides Nucleic Acids 2014;33(10):668-77.PMID:25222520DOI:10.1080/15257770.2014.917671.
To extend the potential of 5'-noraristeromycin (and its enantiomer) as potential antiviral candidates, the enantiomers of the carbocyclic 5'-nor derivatives of 5'-methylthio-5'-deoxyadenosine and 5'-phenylthio-5'-deoxyadenosine have been synthesized and evaluated. None of the compounds showed meaningful antiviral activity.