1,5-Isoquinolinediol
(Synonyms: 1,5-二羟基异喹啉,NSC 65585) 目录号 : GC40468An inhibitor of poly(ADP-ribose) polymerases
Cas No.:5154-02-9
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
The poly(ADP-ribose) polymerases (PARPs) form a family of enzymes with roles in DNA repair and apoptosis. [1] 1,5-Isoquinolinediol is an inhibitor of poly(ADP-ribose) synthetase (PARP1; IC50 = 0.39 μM). [2] It has been used to study the role of PARP1 in both DNA repair and oxidant stress-induced cell death. [3][4][5] This compound can be used with cells in culture and in animals.[4][6][7]
Reference:
[1]. Davar, D., Beumer, J.H., Hamieh, L., et al. Role of PARP inhibitors in cancer biology and therapy. Current Medicinal Chemistry 19(23), 3907-3921 (2012).
[2]. Banasik, M., Komura, H., Shimoyama, M., et al. Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. The Journal of Biological Chemisty 267(3), 1569-1575 (1992).
[3]. Ruscetti, T., Lehnert, B.E., Halbrook, J., et al. Stimulation of the DNA-dependent protein kinase by poly(ADP-ribose) polymerase. The Journal of Biological Chemisty 273(23), 14461-14467 (1998).
[4]. Chatterjee, P.K., Zacharowski, K., Cuzzocrea, S., et al. Inhibitors of poly (ADP-ribose) synthetase reduce renal ischemia-reperfusion injury in the anesthetized rat in vivo. The FASEB Journal 14(5), 641-651 (2000).
[5]. Bowes, J., McDonald, M.C., Piper, J., et al. Inhibitors of poly (ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress. Cardiovascular Research 41(1), 126-134 (1999).
[6]. Byun, J.Y., Kim, M.J., Eum, D.Y., et al. Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose) polymerase-1 is required for mitochondrial cell death induced by triterpenoid pristimerin in human cervical cancer cells. Molecular Pharmacology 76(4), 734-744 (2009).
[7]. Kang, Y.H., Yi, M.J., Kim, M.J., et al. Caspase-independent cell death by arsenic trioxide in human cervical cancer cells: Reactive oxygen species-mediated poly(ADP-ribose) polymerase-1 activation signals apoptosis-inducing factor release from mitochondria. Cancer Research 64(24), 8960-8967 (2004).
| Cas No. | 5154-02-9 | SDF | |
| 别名 | 1,5-二羟基异喹啉,NSC 65585 | ||
| 化学名 | 5-hydroxy-1(2H)-isoquinolinone | ||
| Canonical SMILES | OC1=C2C(C(NC=C2)=O)=CC=C1 | ||
| 分子式 | C9H7NO2 | 分子量 | 161.2 |
| 溶解度 | Soluble in DMSO and methanol, insoluble in water | 储存条件 | Store at 4°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 | 6.2035 mL | 31.0174 mL | 62.0347 mL |
| 5 mM | 1.2407 mL | 6.2035 mL | 12.4069 mL |
| 10 mM | 0.6203 mL | 3.1017 mL | 6.2035 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。
The Poly(ADP-Ribose)Polymerase-1 Inhibitor 1,5-Isoquinolinediol Attenuate Diabetes-Induced NADPH Oxidase-Derived Oxidative Stress in Retina
J Ocul Pharmacol Ther 2018 Sep;34(7):512-520.PMID:29912609DOI:10.1089/jop.2017.0117.
Purpose: To examine the effects of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitor 1,5-Isoquinolinediol (IQ) on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived oxidative stress in diabetic retina. Methods: Streptozotocin-induced diabetic rats were treated with IQ. The NADPH oxidase enzyme activity was determined by luminometer. Expression of gp91phox, P47phox and nitrated proteins was examined by western blot. Interaction between gp91phox and P47phox was determined by coimmunoprecipitation. Enzyme-linked immunosorbent assay was utilized to measure the level of retinal total antioxidant capacity. We also studied the effect of the IQ on hydrogen peroxide (H2O2)-induced cleavage of PARP-1 and caspase-3 in human retinal Müller glial cells. Results: Treatment of retinal Müller cells with H2O2-induced PARP-1 and caspase-3 cleavage that was attenuated by IQ cotreatment. Diabetes upregulated PARP-1, NADPH oxidase enzyme activity, gp91phox, P47phox, nitrated protein expression and interaction between gp91phox and P47phox, and downregulated total antioxidant capacity in the retinas compared with nondiabetic rats. Administration of IQ did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of NADPH oxidase enzyme activity and expressions of gp91phox, P47phox, and nitrated proteins and interaction between gp91phox and P47phox. In addition, IQ ameliorated diabetes-induced downregulation of total antioxidant capacity in the retina. Conclusion: PARP-1 inhibition by IQ protects diabetic retina from NADPH oxidase-derived oxidative stress. Thus, inhibition of PARP-1 could have potential therapeutic value in preventing the development of diabetic retinopathy.
Pharmacogenomic analysis indicates potential of 1,5-Isoquinolinediol as a universal anti-aging agent for different tissues
Oncotarget 2015 Jul 10;6(19):17251-60.PMID:25980498DOI:10.18632/oncotarget.3949.
The natural aging of multicellular organisms is marked by a progressive decline in the function of cells and tissues. The accumulation of senescent cells in tissues seems to eventually cause aging of the host. Nevertheless, gene expression that influences aging is unlikely to be conserved between tissues, and age-related loss of function seems to depend on a variety of mechanisms. This is a concern when developing anti-aging drugs in geriatric clinical pharmacology. We have sought a universal agent to redundantly cover gene expression despite the variation in differentially expressed genes between tissues. Using a minimally modified connectivity map, the poly (ADP-ribose) polymerase (PARP) inhibitor 1,5-Isoquinolinediol was selected as a potent candidate, simultaneously applicable to various tissues. This choice was validated in vitro. Treatment of murine embryonic fibroblasts with 1,5-Isoquinolinediol appeared to efficiently suppress the rate of replicative senescence at a concentration of 0.1 µM without resulting in cell death. The appearance of abnormal nuclei and accumulation of β-galactosidase in the cytoplasm were inhibited by daily treatment with the agent. When the aging process was accelerated by hydroxyurea-induced oxidative stress, the effect was even more noticeable. Thus, 1,5-Isoquinolinediol may potentially be developed as an agent to prolong life.
1,5-Isoquinolinediol increases the frequency of gene targeting by homologous recombination in mouse fibroblasts
Biochem Cell Biol 2003 Feb;81(1):17-24.PMID:12683632DOI:10.1139/o02-172.
Gene targeting is a technique that allows the introduction of predefined alterations into chromosomal DNA. It involves a homologous recombination reaction between the targeted genomic sequence and an exogenous targeting vector. In theory, gene targeting constitutes the ideal method of gene therapy for single gene disorders. In practice, gene targeting remains extremely inefficient for at least two reasons: very low frequency of homologous recombination in mammalian cells and high proficiency of the mammalian cells to randomly integrate the targeting vector by illegitimate recombination. One known method to improve the efficiency of gene targeting is inhibition of poly(ADP-ribose)polymerase (PARP). It has been shown that PARP inhibitors, such as 3-methoxybenzamide, could lower illegitimate recombination, thus increasing the ratio of gene targeting to random integration. However, the above inhibitors were reported to decrease the absolute frequency of gene targeting. Here we show that treatment of mouse Ltk cells with 1,5-Isoquinolinediol, a recent generation PARP inhibitor, leads to an increase up to 8-fold in the absolute frequency of gene targeting in the correction of the mutation at the stable integrated HSV tk gene.
Reversal of neurobehavioral and neurochemical alterations in STZ-induced diabetic rats by FeTMPyP, a peroxynitrite decomposition catalyst and 1,5-Isoquinolinediol a poly(ADP-ribose) polymerase inhibitor
Neurol Res 2014 Jul;36(7):619-26.PMID:24620961DOI:10.1179/1743132813Y.0000000301.
Objective: In this study, we have evaluated the involvement of nitrosative stress and poly-ADP ribosyl polymerase (PARP) in diabetes induced neurobehavioral and neurochemical changes using pharmacological agents peroxynitrite decomposition catalyst (FeTMPyP) and a PARP inhibitor (1,5-Isoquinolinediol) in diabetic brains. Methods: The extent of neurobehavioral changes was assessed by functional observation battery, motor coordination activity (rota rod performance) and passive avoidance test. Neurochemical changes were assessed by measuring nicotinamide adenine dinucleotide (NAD), malondialdehyde, acetylcholinesterase, neurotransmitters (GABA and glutamate) levels in the hippocampus. GABA and glutamate were measured by high-performance liquid chromatography with electrochemical detection method. Results: Two weeks' treatment with FeTMPyP (3 mg/kg, i.p.) and 1,5-Isoquinolinediol (3 mg/kg, i.p.) improved the cognitive deficits in diabetic rats as observed in passive avoidance test. Both the agents inhibited lipid peroxidation and improves the acetylcholinesterase level in the hippocampus. 1,5-Isoquinolinediol treatment also improves the NAD, neurotransmitter level in the hippocampus. Discussion: These results suggest that peroxynitrite decomposition catalyst and PARP inhibitor have beneficial effects in neurobehavioral alterations induced by diabetes. Improvement in neurobehavioral alteration may be attributed to reversal of neurotransmitter homeostasis deficits.
Poly(ADP-ribose) polymerase inhibitors counteract diabetes- and hypoxia-induced retinal vascular endothelial growth factor overexpression
Int J Mol Med 2004 Jul;14(1):55-64.PMID:15202016doi
We hypothesize that poly(ADP-ribose) polymerase (PARP) activation is an important mechanism in the oxidative stress-related development of diabetic retinopathy. In the experiments reported here, we evaluated if: a) PARP activation is present in the retina in short-term diabetes; and b) PARP inhibitors, 3-aminobenzamide and 1,5-Isoquinolinediol, counteract diabetes- and hypoxia-induced retinal VEGF formation. In vivo studies were performed in control and streptozotocin-diabetic rats treated with/without 3-aminobenzamide or 1,5-Isoquinolinediol (30 and 3 mg/kg per day, intraperitoneally, for 2 weeks after 2 weeks of diabetes). In vitro studies were performed in human retinal pigment epithelial cells exposed to normoxia or hypoxia with/without 3-aminobenzamide and 1,5-Isoquinolinediol at 200 and 2 micro M. Retinal immunostaining for poly(ADP-ribose) was increased and NAD concentration reduced in diabetic rats, and both variables were corrected by PARP inhibitors. Retinal VEGF protein (ELISA, immunohistochemistry), but not mRNA (ribonuclease protection assay) abundance, was increased in diabetic rats, and this increase was corrected by both 3-aminobenzamide and 1,5-Isoquinolinediol. PARP inhibitors did not affect retinal glucose, sorbitol pathway intermediates or lipid peroxidation in diabetic rats. Hypoxia caused a several-fold increase in both VEGF-mRNA and protein in retinal pigment epithelial cells. VEGF mRNA overexpression was only slighly blunted by PARP inhibitors whereas VEGF protein was corrected. In conclusion, PARP is involved in diabetes- and hypoxia-induced VEGF production at post-transcriptional level, downstream from the sorbitol pathway activation and oxidative stress. The results justify studies of PARP inhibitors in models of retinopathy of prematurity and diabetic retinopathy.