Atpenin A5
(Synonyms: 抗癣青霉素A5) 目录号 : GC42869
A specific inhibitor of mitochondrial complex II enzymes
Cas No.:119509-24-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mitochondrial complex II (succinate dehydrogenase or succinate:ubiquinone oxidoreductase) is a functional member of the Krebs cycle and the aerobic respiratory chain that couples the oxidation of succinate to fumarate with the reduction of quinone to quinol. Atpenin A5, an antifungal antibiotic isolated from Penicillium sp. found in soil, is a highly specific ubiquinone-binding site inhibitor of succinate dehydrogenase (IC50s = 12 and 3.7 nM in nematode and mammalian mitochondria, respectively, versus IC50s > 100 μM for inhibition of complex I and complex III enzymes). Atpenin A5 has cardioprotective effects against simulated ischemia-reperfusion injury in cardiomyocytes. Several mechanisms through which this occurs, including activation of mitochondrial ATP-sensitive potassium channels or modulation of mitochondrial reactive oxygen species generation, have been proposed.
| Cas No. | 119509-24-9 | SDF | |
| 别名 | 抗癣青霉素A5 | ||
| Canonical SMILES | COC(NC(O)=C1C([C@H](C[C@H](C)[C@H](CCl)Cl)C)=O)=C(OC)C1=O | ||
| 分子式 | C15H21Cl2NO5 | 分子量 | 366.2 |
| 溶解度 | DMSO: Soluble,Ethanol: Soluble,Methanol: Soluble | 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 | 2.7307 mL | 13.6537 mL | 27.3075 mL |
| 5 mM | 0.5461 mL | 2.7307 mL | 5.4615 mL |
| 10 mM | 0.2731 mL | 1.3654 mL | 2.7307 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。
Enantioselective total synthesis of Atpenin A5
J Antibiot (Tokyo) 2009 Jun;62(6):289-94.PMID:19373276DOI:10.1038/ja.2009.29.
Enantioselective total synthesis of Atpenin A5, a potent mitochondrial complex II (succinate-ubiquinone oxidoreductase) inhibitor, has been achieved by a convergent approach through a coupling reaction between 5-iodo-2,3,4,6-tetraalkoxypyridine and a side-chain aldehyde. The two key segments were synthesized through ortho-metalation/boronation with (MeO)3B/oxidation with mCPBA, ortho-iodination, halogen dance reaction, Sharpless epoxidation and regioselective epoxide-opening reaction. This synthetic study resulted in the revision of the earlier reported 1H-NMR data of the natural Atpenin A5 and the confirmation of the stereochemical assignment.
Synthesis and Antineoplastic Evaluation of Mitochondrial Complex II (Succinate Dehydrogenase) Inhibitors Derived from Atpenin A5
ChemMedChem 2017 Jul 6;12(13):1033-1044.PMID:28523727DOI:10.1002/cmdc.201700196.
Mitochondrial complex II (CII) is an emerging target for numerous human diseases. Sixteen analogues of the CII inhibitor natural product Atpenin A5 were prepared to evaluate the structure-activity relationship of the C5 pyridine side chain. The side chain ketone moiety was determined to be pharmacophoric, engendering a bioactive conformation. One analogue, 1-(2,4-dihydroxy-5,6-dimethoxypyridin-3-yl)hexan-1-one (16 c), was found to have a CII IC50 value of 64 nm, to retain selectivity for CII over mitochondrial complex I (>156-fold), and to possess a ligand-lipophilicity efficiency (LLE) of 5.62, desirable metrics for a lead compound. This derivative and other highly potent CII inhibitors show potent and selective anti-proliferative activity in multiple human prostate cancer cell lines under both normoxia and hypoxia, acting to inhibit mitochondrial electron transport.
Bioisosteric Exchange of Csp3 -Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues
Angew Chem Int Ed Engl 2016 Mar 14;55(12):4049-53.PMID:26891236DOI:10.1002/anie.201511672.
Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, Atpenin A5, are described. These analogues were selected on the basis of Cl→CH3 or H3 C→Cl exchanges in the side-chain of Atpenin A5. The interchange of chloro and methyl substituents led to complex II inhibitors with equal IC50 values. This suggests that Cl↔Me bioisosteric exchange can be realized in aliphatic settings.
The complex II inhibitor Atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial KATP channels
Basic Res Cardiol 2009 Mar;104(2):121-9.PMID:19242645DOI:10.1007/s00395-009-0001-y.
The cardioprotective effects of ischemic preconditioning (IPC) can be mimicked or blocked by pharmacologic agents, which modulate the mitochondrial ATP-sensitive potassium (mK(ATP)) channel, thereby implicating this channel in the mechanism of IPC. Cardioprotection can also be achieved via inhibition of mitochondrial respiratory complex II, and significant pharmacologic overlap exists between complex II inhibitors and mK(ATP) channel agonists. However, the relationship between complex II and the mK(ATP) channel remains unclear. Atpenin A5 (AA5) is a potent and specific complex II inhibitor, and herein we report that AA5 (1 nM) also activates the mK(ATP) channel and protects against simulated ischemia-reperfusion (IR) injury in isolated cardiomyocytes. Similar to known mK(ATP) agonists, AA5-mediated protection was sensitive to the mK(ATP) antagonists 5-hydroxydecanoate (5HD) and glyburide. Notably, the optimal mK(ATP) opening and protective concentration of AA5 had no effect on complex II enzymatic activity, suggesting an interaction of AA5 with complex II, but not inhibition of the complex per se, is necessary for protection. A cardioprotective effect of AA5 was also observed in isolated perfused hearts, wherein AA5 increased post-IR contractile function and decreased infarct size, in a 5HD-sensitive manner. In conclusion, the specific complex II inhibitor AA5 is the most potent mK(ATP) activator discovered to date, and provides a novel method of activating mK(ATP) channels and protecting the heart from IR injury.
Synthetic atpenin analogs: Potent mitochondrial inhibitors of mammalian and fungal succinate-ubiquinone oxidoreductase
Bioorg Med Chem Lett 2010 Mar 1;20(5):1665-8.PMID:20137945DOI:10.1016/j.bmcl.2010.01.066.
Atpenins and harzianopyridone represent a unique class of penta-substituted pyridine-based natural products that are potent inhibitors of complex II (succinate-ubiquinone oxidoreductase) in the mitochondrial respiratory chain. These compounds block electron transfer in oxidative phosphorylation by inhibiting oxidation of succinate to fumarate and the coupled reduction of ubiquinone to ubiquinol. From our investigations of complex II inhibitors as potential agricultural fungicides, we report here on the synthesis and complex II inhibition for a series of synthetic atpenin analogs against both mammalian and fungal forms of the enzyme. Synthetic atpenin 2e provided optimum mammalian and fungal inhibition with slightly higher potency than natural occurring Atpenin A5.