CGS 21680 HCl
目录号 : GC11978
CGS 21680 HCl是一种选择性腺苷A2A受体激动剂，IC50值为22nM。
Cas No.:124431-80-7
Sample solution is provided at 25 µL, 10mM.
CGS 21680 HCl is a selective adenosine A2A receptor agonist with an IC50 value of 22nM[1].CGS 2168 enhances the release of excitatory transmitter amino acids in the ischemic rat cerebral cortex[2]. CGS 21680 HCl accelerates the resequestration of cytoplasmic calcium and inhibits the proinflammatory activity of human neutrophils[3].
In vitro, CGS 21680 HCl (1µM) treatment of human urothelial cell line (UROtsa cells) and human neutrophils for 3h significantly reduced cell migration induced by uropathogenic Escherichia coli (UPEC)[4].
In vivo, CGS 21680 HCl (0.1mg/kg) treated humanized NSG mice by intraperitoneal injection had a dual effect, increasing weight loss, reducing T cells, and increasing serum human IL-6 concentrations, but reducing hepatic leukocyte infiltration and serum human TNF-α concentrations[5]. CGS 21680 HCl (0.1mg/kg) was intraperitoneally injected into mice with pleurisy, which significantly reduced the levels of inflammatory factors, neutrophil infiltration and the extent of lung injury[6]. CGS 21680 HCl (0.1mg/kg) was intraperitoneally injected into mice with spinal cord injury, which reduced tissue damage, influx of myeloperoxidase-positive leukocytes, nuclear factor-κB activation and iNOS expression in spinal cord tissue, and reduced JNK MAPK activation in spinal cord oligodendrocytes[7].
References:
[1] Varani K, Gessi S, Merighi S, et al. Adenosine A2A receptors of human circulating blood elements[J]. Drug development research, 1998, 45(3‐4): 253-260.
[2] O'regan M H, Simpson R E, Perkins L M, et al. The selective A2 adenosine receptor agonist CGS 21680 HCl enhances excitatory transmitter amino acid release from the ischemic rat cerebral cortex[J]. Neuroscience letters, 1992, 138(1): 169-172.
[3] Anderson R, Visser S S, Ramafi G, et al. Accelerated resequestration of cytosolic calcium and suppression of the pro‐inflammatory activities of human neutrophils by CGS 21680 HCl in vitro[J]. British journal of pharmacology, 2000, 130(4): 717-724.
[4] Säve S, Mohlin C, Vumma R, et al. Activation of adenosine A2A receptors inhibits neutrophil transuroepithelial migration[J]. Infection and immunity, 2011, 79(8): 3431-3437.
[5] Geraghty N J, Adhikary S R, Watson D, et al. The A2A receptor agonist CGS 21680 HCl has beneficial and adverse effects on disease development in a humanised mouse model of graft-versus-host disease[J]. International Immunopharmacology, 2019, 72: 479-486.
[6] Impellizzeri D, Di Paola R, Esposito E, et al. CGS 21680 HCl, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation[J]. European journal of pharmacology, 2011, 668(1-2): 305-316.
[7] Genovese T, Melani A, Esposito E, et al. The selective adenosine A2A receptor agonist CGS 21680 HCl reduces JNK MAPK activation in oligodendrocytes in injured spinal cord[J]. Shock, 2009, 32(6): 578-585.
CGS 21680 HCl HCl是一种选择性腺苷A2A受体激动剂，IC50值为22nM[1]。CGS 2168能够增强缺血大鼠大脑皮层的兴奋性递质氨基酸释放[2]。CGS 21680 HCl HCl能够加速胞质钙的再隔离和抑制人中性粒细胞的促炎活性[3]。
在体外，CGS 21680 HCl HCl（1µM）处理人尿路上皮细胞系（UROtsa细胞）和人中性粒细胞3h，显著减少了尿路致病性大肠杆菌（UPEC）引起的细胞迁移[4]。
在体内，CGS 21680 HCl HCl（0.1mg/kg）通过腹腔注射治疗人源化NSG小鼠，具有双重影响作用，增加了体重减轻，减少了T细胞，增加了血清人IL-6浓度，但减少了肝白细胞浸润和血清人TNF-α浓度[5]。CGS 21680 HCl HCl（0.1mg/kg）通过腹腔注射治疗胸膜炎小鼠，显著降低了炎症因子水平，减少了中性粒细胞浸润和肺损伤的程度[6]。CGS 21680 HCl HCl（0.1mg/kg）通过腹腔注射治疗脊髓损伤小鼠，减少了脊髓组织中组织损伤、髓过氧化物酶阳性白细胞的内流、核因子-κB活化和iNOS表达，降低脊髓少突胶质细胞中的JNK MAPK活化[7]。
| Cell experiment [1]: | |
Cell lines | UROtsa cells、human neutrophils |
Preparation Method | Serum-free culture medium (without penicillin and streptomycin) containing 108 CFU/ml of UPEC strain IA2 was added to the bottom well of transwell inserts for 24h. Bacterial multiplication was limited by incubating the UROtsa cells with gentamicin (50μg/mL) 24h prior to infection. Human neutrophils were prepared as described above, and 3×106 neutrophils were added to the top well. Samples were taken from the bottom well after 0, 1, 2, and 3h. The number of neutrophils that had migrated was counted in a Bürker chamber. To examine the role of adenosine receptor activation in transuroepithelial neutrophil migration, adenosine (10μM) or the specific A2A receptor agonist CGS 21680 HCl (1μM) was added to the top well together with neutrophils after 24h of UPEC infection. |
Reaction Conditions | 1µM; 3h |
Applications | When cells were stimulated with the A2A receptor agonist CGS 21680 HCl, UPEC-evoked migration was significantly decreased after 1h and 2h. |
| Animal experiment [2]: | |
Animal models | NSG mice |
Preparation Method | Female NSG mice aged 6–8 weeks were injected i.p. daily (day 2 to day 11) with saline/0.2% DMSO (vehicle) or vehicle containing CGS 21680 HCl (0.1mg/kg). hPBMCs, isolated by density centrifuga tion using Ficoll-Paque PLUS and resuspended in Dulbecco's phosphate-buffer saline , were injected i.p. (day 0) (10×106 hPBMCs/mouse). At 3 weeks post-hPBMC injection, mice were checked for en graftment by immunophenotyping of tail vein blood. Mice were monitored for signs of GVHD using a scoring system, giving a total clinical score out of 10. Mice were euthanized at 10weeks post-injection of hPBMCs, or earlier if exhibiting a clinical score of ≥8 or a weight loss of ≥10%, according to the approved animal ethics protocol. |
Dosage form | 0.1mg/kg; i.p. |
Applications | CGS 21680 HCl increased weight loss, and failed to reduce the clinical score or increase survival in this humanised mouse model of GVHD. CGS 21680 HCl reduced T regulatory cells and increased serum human IL-6 concentrations. CGS 21680 HCl reduced serum human tumor necrosis factor (TNF)-α concentrations and leukocyte infiltration into the liver. |
References: | |
| Cas No. | 124431-80-7 | SDF | |
| 化学名 | 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid;hydrochloride | ||
| Canonical SMILES | CCNC(=O)C1C(C(C(O1)N2C=NC3=C2N=C(N=C3N)NCCC4=CC=C(C=C4)CCC(=O)O)O)O.Cl | ||
| 分子式 | C23H30ClN7O6 | 分子量 | 535.98 |
| 溶解度 | ≥ 53.6mg/mL in DMSO | 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 | 1.8657 mL | 9.3287 mL | 18.6574 mL |
| 5 mM | 0.3731 mL | 1.8657 mL | 3.7315 mL |
| 10 mM | 0.1866 mL | 0.9329 mL | 1.8657 mL |
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| 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 |
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| % 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。
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2.
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Quality Control & SDS
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- Purity: >98.00%
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