5-AIQ
(Synonyms: 5-Aminoisoquinolin-1-one) 目录号 : GC681615-AIQ (5-Aminoisoquinolin-1-one) 是一种水溶性的 PARP-1 抑制剂。5-AIQ 是多种药物中的一个重要官能团。5-AIQ 减少肝脏缺血再灌注相关的组织损伤，可用于肝脏缺血再灌注相关治疗条件的研究。
Cas No.:93117-08-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
5-AIQ (5-Aminoisoquinolin-1-one) is a water-soluble PARP-1 inhibitor. 5-AIQ is an important functional group in various drugs. 5-AIQ reduces the tissue injury associated with ischemia-reperfusion of the liver, it can be used for the research of the therapy conditions associated with ischemia-reperfusion of the liver[1][2].
5-AIQ (5000 μg) significantly reduces the number of colonies of TA 98 without metabolic activation, and TA 98 and TA 1537 with metabolic activation[1].
5-AIQ (150 and 250 mg/kg; p.o.; once) possess no significantly genotoxic in vivo system by micronucleus test[1].
5-AIQ (3 mg/kg; p.o.; 5 min prior to onset of liver ischemia) reduces the tissue injury associated with ischemia-reperfusion of the liver[2].
| Animal Model: | Male mice[1] |
| Dosage: | 150 and 250 mg/kg |
| Administration: | Oral administration; 150 and 250 mg/kg; once |
| Result: | Showed no increase of micronucleated polychromatic erythrocytes (MNPCE) in both 24 h and 48 h after both 125 and 250 mg/kg duration exposure as compared to the corresponding control. |
| Animal Model: | Anesthetised male Wistar rats with liver ischemia (for 30 minutes) and reperfusion (for 2 hours) [2] |
| Dosage: | 3 mg/kg |
| Administration: | Intravenous injection; 3 mg/kg; 5 min prior to onset of liver ischemia |
| Result: | Reduced PARP activation and showed less staining for ICAM-1. |
[1]. Vinod KR, Chandra S, Sharma SK. Evaluation of 5-aminoisoquinoline (5-AIQ), a novel PARP-1 inhibitor for genotoxicity potential in vitro and in vivo. Toxicol Mech Methods. 2010 Feb;20(2):90-5.
[2]. Mota-Filipe H, et al. The novel PARP inhibitor 5-aminoisoquinolinone reduces the liver injury caused by ischemia and reperfusion in the rat. Med Sci Monit. 2002 Nov;8(11):BR444-53.
| Cas No. | 93117-08-9 | SDF | Download SDF |
| 别名 | 5-Aminoisoquinolin-1-one | ||
| 分子式 | C9H8N2O | 分子量 | 160.17 |
| 溶解度 | 储存条件 | 4°C, protect from light | |
| 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 | 6.2434 mL | 31.2168 mL | 62.4337 mL |
| 5 mM | 1.2487 mL | 6.2434 mL | 12.4867 mL |
| 10 mM | 0.6243 mL | 3.1217 mL | 6.2434 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。
5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)
Curr Med Chem 2015;22(33):3807-29.PMID:26429070DOI:10.2174/0929867322666151002110602.
5-Aminoisoquinolin-1-one (5-AIQ) is a water-soluble inhibitor of the poly(ADPribose) polymerases (PARPs), lacking isoform-selectivity. Although of only moderate potency in vitro against PARP-1, it is highly active in many assays in cells and in models in vivo, indicating excellent uptake. Optimisation of the several synthetic sequences to 5-AIQ has led to development of a short and efficient route from 1-chloroisoquinoline. It has been used widely as a biochemical and pharmacological tool to study the effects of inhibition of the PARPs. It ameliorates the damage to cells and tissues following reperfusion of ischaemic tissue, showing significant protective activity in a rodent model of haemorrhagic shock at the remarkably low dose of 30 µg Kg(-1). Protection is also seen in models of myocardial infarction, ischaemic kidney and liver disorders, stroke and organ transplantation. Inhibition of PARP-1 by 5-AIQ causes down-regulation of the activity of NF-κB, which then down-regulates the expression of several gene products. Thus 5-AIQ has anti-inflammatory activity in vivo, through modulating the expression of cytokines and adhesion molecules. This indirect inhibition of expression is relevant in the activity of 5-AIQ in models of arthritis, Parkinson's disease, multiple sclerosis, spinal cord injury, periodontitis and inflammatory conditions of the lung. Inhibition of expression of matrix metalloproteinases and other factors gives rise to anti-angiogenic activity and to remarkable anti-metastatic activity in a mouse model. Thus, although it has been overtaken by other PARP-inhibiting drugs in the oncological clinic, 5-AIQ remains a valuable tool to study the roles of PARPs in health and in diverse diseases.
5-AIQ inhibits H2O2-induced apoptosis through reactive oxygen species scavenging and Akt/GSK-3β signaling pathway in H9c2 cardiomyocytes
Toxicol Appl Pharmacol 2013 Apr 1;268(1):90-8.PMID:23352507DOI:10.1016/j.taap.2013.01.004.
Poly(adenosine 5'-diphosphate ribose) polymerase (PARP) is a nuclear enzyme activated by DNA strand breaks and plays an important role in the tissue injury associated with ischemia and reperfusion. The aim of the present study was to investigate the protective effect of 5-aminoisoquinolinone (5-AIQ), a PARP inhibitor, against oxidative stress-induced apoptosis in H9c2 cardiomyocytes. 5-AIQ pretreatment significantly protected against H2O2-induced cell death, as determined by the XTT assay, cell counting, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and Western blot analysis of apoptosis-related proteins such as caspase-3, Bax, and Bcl-2. Upregulation of antioxidant enzymes such as manganese superoxide dismutase and catalase accompanied the protective effect of 5-AIQ on H2O2-induced cell death. Our data also showed that 5-AIQ pretreatment protected H9c2 cells from H2O2-induced apoptosis by triggering activation of Akt and glycogen synthase kinase-3β (GSK-3β), and that the protective effect of 5-AIQ was diminished by the PI3K inhibitor LY294002 at a concentration that effectively abolished 5-AIQ-induced Akt and GSK-3β activation. In addition, inhibiting the Akt/GSK-3β pathway by LY294002 significantly attenuated the 5-AIQ-mediated decrease in cleaved caspase-3 and Bax activation and H9c2 cell apoptosis induction. Taken together, these results demonstrate that 5-AIQ prevents H2O2-induced apoptosis in H9c2 cells by reducing intracellular reactive oxygen species production, regulating apoptosis-related proteins, and activating the Akt/GSK-3β pathway.
Evaluation of 5-aminoisoquinoline (5-AIQ), a novel PARP-1 inhibitor for genotoxicity potential in vitro and in vivo
Toxicol Mech Methods 2010 Feb;20(2):90-5.PMID:20102296DOI:10.3109/15376510903572870.
5-aminoisoquinoline (5-AIQ) is an active PARP-1 inhibitor as well as an important functional group various drugs. Quinolines are generally known as mutagenic and carcinogenic in various in vitro and in vivo systems, while both positive and negative findings are available on the mutagenic potential of several isoquinolines. Since no literature is available on the genotoxicity of 5-AIQ, a battery of tests were conducted, in accordance with relevant OECD protocols, such as bacterial reverse mutation test, in vitro chromosomal aberration test, and bone marrow micronucleus test in mouse. These studies demonstrate that 5-AIQ does not possess genotoxic activity both with in vitro and in vivo systems. The findings substantiate the therapeutic value of 5-AIQ.
Influence of 5-aminoisoquinolin-1-one (5-AIQ) on neutrophil chemiluminescence in rats with transient and prolonged focal cerebral ischemia and after reperfusion
J Physiol Pharmacol 2008 Dec;59(4):811-22.PMID:19212013doi
Stimulation of neutrophils by different factors increases their oxidative activity and the free radicals produced can report on the degree of activation. Poly(adenosine 5'-diphosphate ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation. 5-aminoisoquinolin-1-one (5-AIQ) is a potent inhibitor of PARP-1 activity in vitro and in vivo in rats. Acute (80 min) and prolonged (24h) focal cerebral ischaemia was induced in rats by obstruction of the median cerebral artery, with or without reperfusion, with or without administration of 5-AIQ. The oxidative activity of neutrophils was measured by chemiluminescence. Administration of 5-AIQ.HCl (3.0 mg kg(-1) b.w. - i.v.) caused a significant decrease in the oxidative activity of neutrophils in the group which had experienced chronic ischaemia for 24h but had no significant effect in the group which had received 80 min ischaemia, when compared to the control group. Increase of the oxidative activity of neutrophils was confirmed in rats with prolonged cerebral ischaemia, followed by reperfusion. 5-AIQ probably may decrease this activity through inhibition of PARP-1 in focus of local ischaemia as well as hence lowering the expression of inflammatory mediators by activated neutrophils.
One-pot tandem Hurtley-retro-Claisen-cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs
Bioorg Med Chem 2013 Sep 1;21(17):5218-27.PMID:23849206DOI:10.1016/j.bmc.2013.06.031.
Poly(ADP-ribose)polymerase-1 (PARP-1) is an important target for drug design for several therapeutic applications. 5-Aminoisoquinolin-1-one (5-AIQ) is a highly water-soluble lead compound; synthetic routes to 3-substituted analogues were explored. Tandem Hurtley coupling of β-diketones with 2-bromo-3-nitrobenzoic acid, retro-Claisen acyl cleavage and cyclisation gave the corresponding 3-substituted 5-nitroisocoumarins. Treatment with ammonia at high temperature and reduction with tin(II) chloride gave eleven target 3-substituted 5-AIQs, which were all soluble in water (>1% w/v) as their HCl salts. Most were more potent than 5-AIQ as inhibitors of PARP-1 and of PARP-2 in vitro, the most active being 5-amino-3-methylisoquinolin-1-one (PARP-1: IC50=0.23μM vs IC50=1.6μM for 5-AIQ). Some rationalisation of the SAR was achieved through molecular modelling.