Istradefylline(KW-6002) (Synonyms: KW 6002) |
| رقم الكتالوجGC11590 |
إستراديفيلين (KW-6002) هو مضاد قوي وانتقائي لمستقبلات الأدينوزين A2A، وهو فعال عن طريق الفم، وله تأثير كبير في نماذج التجارب المخبرية لداء باركنسون حيث يصل قطرانه إلى 2.2 نانومتر.
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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.
| Cell experiment [1]: | |
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Cell lines |
B16F10 melanoma cells |
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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: |
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| Cas No. | 155270-99-8 | SDF | |
| المرادفات | KW 6002 | ||
| Chemical Name | 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 | ||
| Formula | C20H24N4O4 | M.Wt | 384.43 |
| الذوبان | ≥ 8.8mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6013 mL | 13.0063 mL | 26.0125 mL |
| 5 mM | 520.3 μL | 2.6013 mL | 5.2025 mL |
| 10 mM | 260.1 μL | 1.3006 mL | 2.6013 mL |
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 18 reference(s) in Google Scholar.)
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