AR-A014418
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AR-A014418是一种选择性的GSK-3抑制剂。
糖原合酶激酶-3(GSK3)是一种丝氨酸/苏氨酸激酶,与病理情况,如糖尿病和阿尔茨海默病(AD)相关。
体外实验:ARA014418以ATP竞争性的方式起作用,不能显著抑制cdk2、cdk5或26种其它激酶,表明其对GSK3的高特异性。在稳定表达人四重复tau蛋白的细胞中,ARA014418抑制GSK3对tau蛋白特异性位点(Ser-396)的磷酸化[1]。
体内实验:ARA014418可引起行为改变,其与抗抑郁药物的效应是一致的。在公认的用于检测抗抑郁效应的大鼠强迫游泳实验中,AR-A014418亚急性腹腔注射后减少不动时间。而且,AR-A014418还可减少自发及苯丙胺诱导的活性,支持了该效应的特异性[2]。
参考文献:
[1] Bhat R, Xue Y, Berg S, Hellberg S, Orm? M, Nilsson Y, Rades?ter AC, Jerning E, Markgren PO, Borgeg?rd T, Nyl?f M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45.
[2] Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90.
- 1. Sergey V. Rozhkov, Kristina A. Sharlo, et al. "The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions." Int J Mol Sci. 2022 Mar 2;23(5):2751. PMID:35269893
- 2. Jing‐Ting Chiou, Nan‐Chieh Huang, et al. "NOXA-mediated degradation of MCL1 and BCL2L1 causes apoptosis of daunorubicin-treated human acute myeloid leukemia cells." J Cell Physiol. 2021 Nov;236(11):7356-7375. PMID:33982799
- 3. Qiang Li, Dongmei Yu, et al. "TIPE3 promotes non-small cell lung cancer progression via the protein kinase B/extracellular signal-regulated kinase 1/2-glycogen synthase kinase 3β-β-catenin/Snail axis." Transl Lung Cancer Res. 2021 Feb;10(2):936-954. PMID:33718034
- 4. Binyan Lin, Yongxu Li, et al. "CRMP2 is a therapeutic target that suppresses the aggressiveness of breast cancer cells by stabilizing RECK." Oncogene. 2020 Sep;39(37):6024-6040. PMID:32778769
- 5. Lee YC, Shi YJ, et al. "GSK3β suppression inhibits MCL1 protein synthesis in human acute myeloid leukemia cells." J Cell Physiol. 2020;10.1002/jcp.29884. PMID:32572959
- 6. Huang CH, Lee YC, et al. "Arsenic trioxide-induced p38 MAPK and Akt mediated MCL1 downregulation causes apoptosis of BCR-ABL1-positive leukemia cells." Toxicol Appl Pharmacol. 2020;397:115013. PMID:32305283
- 7. Chen YJ, Huang CH, et al. "The suppressive effect of arsenic trioxide on TET2-FOXP3-Lyn-Akt axis-modulated MCL1 expression induces apoptosis in human leukemia cells." Toxicol Appl Pharmacol. 2018 Nov 1;358:43-55. PMID:30213730
- 8. Lee YC, Chen YJ, et al. "Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1." Apoptosis. 2016 Oct 19. PMID:27757735
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 308.31 |
Cas No. | 487021-52-3 |
Formula | C12H12N4O4S |
Synonyms | AR-AO 14418;AR 0133418;AR 014418;GSK 3β inhibitor |
Solubility | insoluble in EtOH; insoluble in H2O; ≥15.4 mg/mL in DMSO |
Chemical Name | 1-[(4-methoxyphenyl)methyl]-3-(5-nitro-1,3-thiazol-2-yl)urea |
SDF | Download SDF |
Canonical SMILES | COC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-] |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
酶学实验 [1]: | |
激酶检测 |
酶学竞争性试验中考察了10个抑制剂浓度,复孔。2 微摩尔生物素化生肽底物加入到包含6毫单位的人重组GSK3酶、12毫摩尔MOPS,pH 7.0、0.3毫摩尔EDTA、0.01% β-巯基乙醇, 0.004% Brij 35, 0.5% 甘油, and 0.5 微克 小牛血清白蛋白的缓冲液中。通过加入25微升含有0.04 μCi of [-33P]ATP已经未标记的ATP的50毫摩尔Mg(Ac)2溶液起始反应。室温孵育29分钟后,加入25微升含有5毫摩尔EDTA、50微摩尔ATP、0.1% Triton X-100以及0.25毫克链霉亲和素包被的SPA终止反应。 |
细胞实验 [1]: | |
细胞系 |
稳定表达4-重复tau蛋白的3T3成纤维细胞 |
溶解方法 |
在DMSO中的溶解度> 15.4 mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
100 nM到50 μM;孵育24小时 |
应用 |
在稳定表达4-重复tau蛋白的人3T3成纤维细胞中,AR-A014418能够抑制tau蛋白在GSK3的特定位点磷酸化。AR-A014418也能通过抑制磷脂酰肌醇3激酶/蛋白激酶B通路防止N2A成神经细胞瘤细胞死亡。 |
动物实验 [2]: | |
动物模型 |
雄性SD大鼠 |
剂量 |
30 μmol/kg,腹腔注射 |
应用 |
亚急性腹膜内注射AR-A014418能够减少暴露于强制游泳试验的大鼠的静止时间,这是一种成熟的抗抑郁药功效模型。 此外,研究表明AR-A014418能降低自发以及安非他明诱导的大鼠活性,该发现也支持了该效应的特异性。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Bhat R, Xue Y, Berg S, Hellberg S, Orm M, Nilsson Y, Radester AC, Jerning E, Markgren PO, Borgegrd T, Nylf M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45. [2] Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90. |
描述 | AR-A014418是一种ATP竞争性的和选择性的GSK3β抑制剂,IC50和Ki值分别为104 nM和38 nM。 | |||||
靶点 | GSK-3 | |||||
IC50 | 104 +/- 27 nM |
质量控制和MSDS
- 批次: