| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
S-adenosylhomocysteine hydrolase (AHCY)
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| ln Vitro |
The IC50 value of Aristeromycin against AHCY is 38.5 nM (nearly equivalent to Km: 48 μM) at 50 μM S-adenosylhomocysteine (SAH), but is 271 nM with 1000 μM SAH (20× Km). After 60 minutes of preincubation, the average IC50 value of Aristeromycin at 50 μM SAH is 12.7 nM[1]. The IC50 value of aristeromycin for LNCaP-FGC cell growth is 3.2 μM, whereas the IC50 value for LNCaP-hr cell growth is 0.88 μM [1]. Aristeromycin can modulate the expression of oncogenic EZH2, at least in part, via activating miR-26a [1].
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. [1] |
| Cell Assay |
A differential cytotoxicity screen for hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells identified Aristeromycin, a derivative of DZNeP. This compound did not show growth inhibition of MRC5 cells. Treatment of cancer cells with DZNeP caused accumulation of SAH and decreases in homocysteine and histone H3K27 methylation. As AHCY gene overexpression has been observed in several cancers, AHCY is considered a therapeutic target...[1]
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| Toxicity/Toxicokinetics |
mouse LD50 intravenous 50 mg/kg CRC Handbook of Antibiotic Compounds, Vols.1- , Berdy, J., Boca Raton, FL, CRC Press, 1980, 5(307), 1981
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| References | |
| Additional Infomation |
Aristeromycin is a member of purines and a nucleoside analogue.
Aristeromycin has been reported in Streptomyces citricolor and Saccharothrix with data available. To find out potent inhibitors of S-adenosylhomocysteine hydrolase (SAHase), several deazaadenosine analogues synthesized in this laboratory and some naturally occurring nucleoside analogues were examined with SAHases from yellow lupin seeds and rabbit liver. Neplanocin A, an antibiotic, inhibited both enzymes more potently than aristeromycin which was also an antibiotic and known as one of the most potent inhibitors of SAHase. The 3-deazaadenine derivatives (2'-deoxy, arabinosyl, xylosyl) inactivated lupin SAHase as potent as 3-deazaadenosine. Whereas, inhibitory activities of 1-deazaadenosine, its derivatives, and 7-deazaadenosine (tubercidin) were very weak.[2] |
| Molecular Formula |
C11H15N5O3
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|---|---|
| Molecular Weight |
265.2685
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| Exact Mass |
265.117
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| CAS # |
19186-33-5
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| PubChem CID |
65269
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| Appearance |
White to off-white solid powder
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| Density |
1.92g/cm3
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| Boiling Point |
595.1ºC at 760mmHg
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| Flash Point |
313.7ºC
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| Vapour Pressure |
5.19E-15mmHg at 25°C
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| Index of Refraction |
1.881
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| LogP |
-0.5
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
334
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| Defined Atom Stereocenter Count |
4
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| SMILES |
OC[C@H]1C[C@@H](N2C=NC3=C(N=CN=C23)N)[C@H](O)[C@@H]1O
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| InChi Key |
UGRNVLGKAGREKS-GCXDCGAKSA-N
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| InChi Code |
InChI=1S/C11H15N5O3/c12-10-7-11(14-3-13-10)16(4-15-7)6-1-5(2-17)8(18)9(6)19/h3-6,8-9,17-19H,1-2H2,(H2,12,13,14)/t5-,6-,8-,9+/m1/s1
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| Chemical Name |
(1R,2S,3R,5R)-3-(6-aminopurin-9-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol
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| Synonyms |
aristeromycin; 19186-33-5; Cycloadenosine; NSC 103526; (1R,2S,3R,5R)-3-(6-aminopurin-9-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol; (1R,2S,3R,5R)-3-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)-1,2-cyclopentanediol; 1,2-Cyclopentanediol, 3-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)-, (1R,2S,3R,5R)-; Carbocyclic adenosine;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~188.49 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (9.42 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (9.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 | 0.3770 mL | 1.8849 mL | 3.7697 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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