Dehydroaltenusin
(Synonyms: 脱氢阿霉素) 目录号 : GC35829
Dehydroaltenusin 脱氢阿霉素是真核DNA 聚合酶 α (DNA polymerase α) 的小分子选择性抑制剂，一种由真菌产生的抗生素，其 IC50值为 0.68 μM。 Dehydroaltenusin 对哺乳动物 polα 活性的抑制作用模式对 DNA 模板引物 (Ki=0.23 μM) 是竞争性的，对 2'-脱氧核糖核苷 5'-三磷酸底物是非竞争性的 (Ki=0.18 μM)。Dehydroaltenusin 在 S 期阻止癌细胞周期并触发凋亡 apoptosis。Dehydroaltenusin 在体内具有抗人类腺癌肿瘤的抗肿瘤活性。
Cas No.:31186-13-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dehydroaltenusin is a small molecule selective inhibitor of eukaryotic DNA polymerase α, a type of antibiotic produced by a fungus with an IC50 value of 0.68 μM. The inhibitory mode of action of dehydroaltenusin against mammalian pol α activity is competitive with respect to the DNA template primer (Ki=0.23 µM) and non-competitive with respect to the 2'-deoxyribonucleoside 5'-triphosphate substrate (Ki=0.18 µM)[1].Dehydroaltenusin arrests the cancer cell cycle at the S-phase and triggers apoptosis[1].Dehydroaltenusin possesses anti-tumor activity against human adenocarcinoma tumor in vivo[1]. IC50: 0.68 μM (DNA polymerase α)[1]
Dehydroaltenusin (38.0-44.4 μM; 24 hours) inhibits cell growth in a dose-dependent manner and the LD50 values varies from 38.0 to 44.4 μM[1].Dehydroaltenusin (38.0 μM; 6 hours) inhibits cell growth by blocking the S-phase of DNA replication[1].Dehydroaltenusin (75.0 μM; 24 hours) has a strong apoptotic effect on human cancer cells, DNA ladders can be detected after 12 h of incubation with dehydroaltenusin[1]. Cell Proliferation Assay[1] Cell Line: Human cancer cell line: A549, BALL-1, HeLa and NUGC-3 cells
Dehydroaltenusin (injection; 20 mg/kg; 2-day intervals; 12-39 days) shows suppressed tumor growth from 21 days[1]. Animal Model: Nude mice bearing HeLa solid tumors[1]
[1]. Mizushina Y, et al. Dehydroaltenusin is a specific inhibitor of mammalian DNA polymerase α. Expert Opin Investig Drugs. 2011 Nov;20(11):1523-34.
| Cas No. | 31186-13-7 | SDF | |
| 别名 | 脱氢阿霉素 | ||
| Canonical SMILES | O=C(C(O)=C1)C=C(C2=CC(OC)=CC(O)=C23)[C@@]1(C)OC3=O | ||
| 分子式 | C15H12O6 | 分子量 | 288.25 |
| 溶解度 | Soluble in DMSO | 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 | 3.4692 mL | 17.3461 mL | 34.6921 mL |
| 5 mM | 0.6938 mL | 3.4692 mL | 6.9384 mL |
| 10 mM | 0.3469 mL | 1.7346 mL | 3.4692 mL |
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| 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 |
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| % 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。
Dehydroaltenusin is a specific inhibitor of mammalian DNA polymerase α
Expert Opin Investig Drugs 2011 Nov;20(11):1523-34.PMID:21923630DOI:10.1517/13543784.2011.619977.
Introduction: We carried out a screen for small molecule selective inhibitors of eukaryotic DNA polymerases (pols). Dehydroaltenusin, isolated from a fungus (Alternaria tenuis), was found to be a specific inhibitor of pol α. Areas covered: We succeeded in chemically synthesizing Dehydroaltenusin along with five analogs. Of these compounds, Dehydroaltenusin was the strongest and most specific inhibitor of mammalian pol α, with an IC(50) value of 0.68 μM. The inhibitory mode of action of Dehydroaltenusin against mammalian pol α activity was competitive with respect to the DNA template primer and non-competitive with respect to the 2'-deoxyribonucleoside 5'-triphosphate substrate. Dehydroaltenusin inhibited the cell proliferation of a human cervical cancer cell line, HeLa, by arresting the cells at the S-phase, and preventing the incorporation of thymidine into the cells. These observations indicate that Dehydroaltenusin blocks in vivo DNA replication by inhibiting pol α. Expert opinion: Dehydroaltenusin was effective in suppressing the growth of solid tumors and, therefore, is of interest as a candidate drug for anti-cancer treatment.
Synthesis of fluorinated polycyclic Dehydroaltenusin analogs through hypervalent iodine-catalyzed dearomatization
Org Biomol Chem 2022 Oct 26;20(41):8104-8107.PMID:36205569DOI:10.1039/d2ob01582j.
We developed a method employing stoichiometric meta-chloroperbenzoic acid (m-CPBA) as an oxidant and hydrogen fluoride pyridine (pyr·HF) as a fluoride source with catalytic amounts of iodobenzene (PhI) for the cyclization and fluorination-dearomatization of phenols, leading to a range of fluorocyclohexa-dienones with yields of up to 94%. This reaction provides a convenient method to synthesize fluorine-containing Dehydroaltenusin analogs under mild conditions, and without expensive reagents. These analogs have potential application as inhibitors of DNA polymerase.
Dehydroaltenusin, a mammalian DNA polymerase alpha inhibitor
J Biol Chem 2000 Oct 27;275(43):33957-61.PMID:10942777DOI:10.1074/jbc.M006096200.
Dehydroaltenusin was found to be an inhibitor of mammalian DNA polymerase alpha (pol alpha) in vitro. Surprisingly, among the polymerases and DNA metabolic enzymes tested, Dehydroaltenusin inhibited only mammalian pol alpha. Dehydroaltenusin did not influence the activities of the other replicative DNA polymerases, such as delta and epsilon; it also showed no effect even on the pol alpha activity from another vertebrate (fish) or plant species. The inhibitory effect of Dehydroaltenusin on mammalian pol alpha was dose-dependent, and 50% inhibition was observed at a concentration of 0.5 microm. Dehydroaltenusin-induced inhibition of mammalian pol alpha activity was competitive with the template-primer and non-competitive with the dNTP substrate. BIAcore analysis demonstrated that Dehydroaltenusin bound to the core domain of the largest subunit, p180, of mouse pol alpha, which has catalytic activity, but did not bind to the smallest subunit or the DNA primase p46 of mouse pol alpha. These results suggest that the Dehydroaltenusin molecule competes with the template-primer molecule on its binding site of the catalytic domain of mammalian pol alpha, binds to the site, and simultaneously disturbs dNTP substrate incorporation into the template-primer.
Anti-tumor effects of Dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha
Biochem Biophys Res Commun 2007 Jan 12;352(2):390-6.PMID:17118336DOI:10.1016/j.bbrc.2006.11.021.
In the screening of selective inhibitors of eukaryotic DNA polymerases (pols), Dehydroaltenusin was found to be an inhibitor of pol alpha from a fungus (Alternaria tennuis). We succeeded in chemically synthesizing Dehydroaltenusin, and the compound inhibited only mammalian pol alpha with IC50 value of 0.5 microM, and did not influence the activities of other replicative pols such as pols delta and epsilon, but also showed no effect on pol alpha activity from another vertebrate, fish, or from a plant species. Dehydroaltenusin also had no influence on the other pols and DNA metabolic enzymes tested. The compound also inhibited the proliferation of human cancer cells with LD50 values of 38.0-44.4 microM. In an in vivo anti-tumor assay on nude mice bearing solid tumors of HeLa cells, Dehydroaltenusin was shown to be a promising suppressor of solid tumors. Histopathological examination revealed that increased tumor necrosis and decreased mitotic index were apparently detected by the compound in vivo. Therefore, Dehydroaltenusin could be of interest as not only a mammalian pol alpha-specific inhibitor, but also as a candidate drug for anti-cancer treatment.
The effects of Dehydroaltenusin, a novel mammalian DNA polymerase alpha inhibitor, on cell proliferation and cell cycle progression
Biochim Biophys Acta 2004 Sep 24;1674(2):193-9.PMID:15374623DOI:10.1016/j.bbagen.2004.06.016.
As described previously, a natural product isolated from fungus (Acremonium sp.), Dehydroaltenusin, is an inhibitor of mammalian DNA polymerase alpha in vitro [Y. Mizushina, S. Kamisuki, T. Mizuno, M. Takemura, H. Asahara, S. Linn, T. Yamaguchi, A. Matsukage, F. Hanaoka, S. Yoshida, M. Saneyoshi, F. Sugawara, K. Sakaguchi, Dehydroaltenusin, a mammalian DNA polymerase alpha inhibitor, J. Biol. Chem. 275 (2000) 33957_33961]. In this study, we investigated the interaction of Dehydroaltenusin with lipid bilayers using an in vitro liposome system, which is a model of the cell membrane, and found that approximately 4% of Dehydroaltenusin was incorporated into liposomes. We also investigated the influence of Dehydroaltenusin on cultured cancer cells. Dehydroaltenusin inhibited the growth of HeLa cells with an LD50 value of 38 microM, and as expected, S phase accumulation in the cell cycle. The total DNA polymerase activity of the extract of incubated cells with Dehydroaltenusin was 23% lower than that of nontreated cells. Dehydroaltenusin increased cyclin E and cyclin A levels. In the analysis of the cell cycle using G1/S synchronized cells by employing hydroxyurea, the compound delayed both entry into the S phase and S phase progression. In a similar analysis using G2/M synchronized cells by employing nocodazole, the compound accumulated the cells at G1/S and inhibited entry into the S phase. Thus, the pharmacological abrogation of cell proliferation by Dehydroaltenusin may prove to be an effective chemotherapeutic agent against tumors.