Istradefylline(KW-6002)
(Synonyms: 伊曲茶碱; KW-6002) 目录号 : GC11590
Istradefylline(KW-6002)是一种腺苷A2A受体拮抗剂。Istradefylline通过选择性拮抗腺苷A2A受体并调节基底神经节的间接通路来改善帕金森病患者的运动功能障碍。Istradefylline主要用于治疗帕金森病。
Cas No.:155270-99-8
Sample solution is provided at 25 µL, 10mM.
Istradefylline(KW-6002) is an adenosine A2A receptor antagonist. Istradefylline improves the motor dysfunction of Parkinson's disease patients by selectively antagonizing adenosine A2A receptors and regulating the indirect pathway of the basal ganglia. Istradefylline is mainly used to treat Parkinson's disease [1-4].
In B16F10 melanoma cells, as Istradefylline (20, 40, 80, 160, 320, 640, 1280, and 2560nM, 24h, 48h, and 72h) concentrations increased, there was a sharp, significant fall in the viability of B16F10 cells in culture in the three established exposure periods [5].
In heatstroke rat models, the treatment of heatstroke rats with Istradefylline (0.3mg/kg, iv, 6h) partially, but significantly, improved vascular hyporesponsiveness at 4h after heat stress [6]. In Melanoma B16F10 tumor models, the tumor volume and weight of animals treated with Istradefylline (1mg/mL, iv, 14d) were significantly reduced [7]. In PFC-lesioned rats, the decreased recognition index in PFC-lesioned rats was significantly reversed by the treatment with Istradefylline (0.1mg/kg, po, 60min) [8]. In common marmosets, Istradefylline (10mg/kg, po, 10d) is effective in improving motor function in combination with low dose dopaminergic drug treatment without provoking dyskinesia [9].
References:
[1]. Jenner P, Mori A, Aradi SD, et al. Istradefylline–a first generation adenosine A2A antagonist for the treatment of Parkinson’s disease. Expert Review of Neurotherapeutics. 2021 Mar 4; 21(3): 317-333.
[2]. Dungo R, Deeks ED. Istradefylline: first global approval. Drugs. 2013 Jun; 73: 875-882.
[3]. Ohno Y, Suzuki M, Asada H, et al. In vitro pharmacological profile of KW-6356, a novel adenosine A2A receptor antagonist/inverse agonist. Molecular Pharmacology. 2023 Jun 1; 103(6): 311-324.
[4]. Chen JF, Cunha RA. The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic signalling. 2020 Jun; 16(2): 167-174.
[5]. da Silva JL, Viana AR, Passos DF, et al. Istradefylline modulates purinergic enzymes and reduces malignancy-associated factors in B16F10 melanoma cells. Purinergic Signalling. 2023 Dec; 19(4): 633-650.
[6]. Shih CC, Chen JH, Liao MH, et al. The Effect of Adenosine A2A Receptor Antagonist Istradefylline on Multiple Organ Dysfunction in Heatstroke Rats. Journal of Medical Sciences. 2020 Mar 1; 40(2): 76-82.
[7]. Gutknecht da Silva JL, Passos DF, Cabral FL, et al. Istradefylline induces A2A/P2X7 crosstalk expression inducing pro-inflammatory signal, and reduces AKT/mTOR signaling in melanoma-bearing mice. Medical Oncology. 2023 May 15; 40(6): 178.
[8]. Kadowaki Horita T, Kobayashi M, Mori A, et al. Effects of the adenosine A 2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex. Psychopharmacology. 2013 Dec; 230: 345-352.
[9]. Uchida SI, Soshiroda K, Okita E, et al. The adenosine A2A receptor antagonist, istradefylline enhances the anti-parkinsonian activity of low doses of dopamine agonists in MPTP-treated common marmosets. European Journal of Pharmacology. 2015 Jan 15; 747: 160-165.
Istradefylline(KW-6002)是一种腺苷A2A受体拮抗剂。Istradefylline通过选择性拮抗腺苷A2A受体并调节基底神经节的间接通路来改善帕金森病患者的运动功能障碍。Istradefylline主要用于治疗帕金森病 [1-4]。
在B16F10黑色素瘤细胞中，随着Istradefylline（20、40、80、160、320、640、1280和2560nM，24h、48h和72h）浓度的增加，在三个既定的暴露时间段内，培养的B16F10细胞活力急剧下降 [5]。
在中暑大鼠模型中，使用Istradefylline（0.3mg/kg，ip，6h）治疗中暑大鼠，在热应激后4h，其血管低反应性得到部分显著的改善 [6]。在黑色素瘤B16F10肿瘤模型中，使用Istradefylline（1mg/mL，iv，14d）治疗的动物的肿瘤体积和重量显著减小 [7]。在PFC损伤大鼠中，使用Istradefylline（0.1mg/kg，po，60min）治疗可显著逆转PFC损伤大鼠的识别指数下降 [8]。对于普通狨猴，Istradefylline（10mg/kg，po，10d与低剂量多巴胺能药物联合治疗可有效改善运动功能，且不会引起运动障碍 [9]。
| Cell experiment [1]: | |
Cell lines | B16F10 melanoma cells |
Preparation Method | B16F10 melanoma cell lines were seeded at 1 × 104 cells/well proper medium in 96-well plates. L929 fibroblasts were used as control. Both cultures were exposed to Istradefylline (20, 40, 80, 160, 320, 640, 1280, and 2560nM) |
Reaction Conditions | 20, 40, 80, 160, 320, 640, 1280, and 2560nM; 24h, 48h, and 72h |
Applications | As Istradefylline concentrations increased, there was a sharp, significant fall in the viability of B16F10 cells in culture in the three established exposure periods. |
| Animal experiment [2]: | |
Animal models | Heatstroke rat model |
Preparation Method | The left carotid artery and right jugular vein of rats were cannulated for hemodynamic detection and drug administration. After recovering from the cannulation, the animals were induced to heatstroke by putting in a heating chamber of 42°C (with relative humidity of 40%–60%) till the rectal temperature reached 44.1°C, followed by 0.3mg/kg Istradefylline or vehicle administration (iv for 10min) and observed for 6h. |
Dosage form | 0.3mg/kg; iv; 6h |
Applications | The treatment of heatstroke rats with Istradefylline partially, but significantly, improved vascular hyporesponsiveness at 4h after heat stress. |
References: | |
| Cas No. | 155270-99-8 | SDF | |
| 别名 | 伊曲茶碱; KW-6002 | ||
| 化学名 | 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione | ||
| Canonical SMILES | CCN1C2=C(C(=O)N(C1=O)CC)N(C(=N2)C=CC3=CC(=C(C=C3)OC)OC)C | ||
| 分子式 | C20H24N4O4 | 分子量 | 384.43 |
| 溶解度 | ≥ 8.8mg/mL in DMSO with gentle warming | 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 | 2.6013 mL | 13.0063 mL | 26.0125 mL |
| 5 mM | 0.5203 mL | 2.6013 mL | 5.2025 mL |
| 10 mM | 0.2601 mL | 1.3006 mL | 2.6013 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。
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Quality Control & SDS
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- Purity: >99.50%
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