GSK269962A
(Synonyms: N-[3-[[2-(4-氨基呋咱-3-基)-1-乙基-1H-咪唑并[4,5-C]吡啶-6-基]氧]苯基]-4-[[2-(4-吗啉基)乙基]氧]苯甲酰胺,GSK 269962) 目录号 : GC17936
A ROCK1 and ROCK2 inhibitor
Cas No.:850664-21-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | The enzyme activity and kinetics of the purified ROCK1(3-543) are determined using scintillation proximity assay. In this assay, purified ROCK1 is incubated with peptide substrate (Biotin-Ahx-AKRRLSSLRA-CONH2), and 33ATP and the subsequent incorporation of 33P into the peptide is quantified by streptavidin bead capture. For IC50 determination, test compounds are dissolved at 10 mM in 100% DMSO, with subsequent serial dilution in 100% DMSO. Compounds are typically assayed over an 11-point dilution range with a concentration in the assay of 10 μM to 0.2 nM in 3-fold dilutions. For dose-response curves, data are normalized and expressed as percentage inhibition using the formula 100×[(U-C1)/(C2-C1)], where U is the unknown value, C1 is the average of the high signal (0%) control wells, and C2 is the average of the low signal (100%) control wells. Curve fitting is performed The results for each compound are recorded as pIC50 values[1]. |
Animal experiment: | Rats[1] Male Sprague-Dawley rats (350-400g) are anesthetized with 5% isoflurane in O2 and killed by exsanguination. Aortic rings, approximately 2 to 3 mm in length, are suspended by two 0.1-mm diameter tungsten wire hooks in 10 mL tissue baths containing Krebs of the following composition: 112 mM NaCl, 4.7 mM KCl, 2.5 mM CaCl2, 1.2 mM KH2PO2, 1.2 mM MgSO4, 25 mM NaHCO3, 11.0 mM dextrose, 0.01 mM indomethacin, and 0.01 mM L-NAME. Krebs is maintained at 37°C and aerated with 95% O2, 5% CO2, pH 7.4,. Changes in isometric force are measured under optimal resting tension (1 g) using FT03 force-displacement transducers coupled to model 7D polygraphs. After a 60-min equilibration period, the vessels are treated with standard concentrations of KCl (60 mM) and phenylephrine (1 μM). Cumulative concentration-response curves to phenylephrine are obtained for each tissue by dosing at 0.5-log unit intervals (1 nM to 10 μM). After several washes, each vessel is contracted to equilibrium with an EC80 concentration of phenylephrine, and tone is reversed by adding cumulative amounts of either GSK269962A or SB-772077-B at 0.5-log unit intervals (0.1 nM to 1 μM). Responses are expressed as percentage reversal of the tone established with phenylephrine. |
References: [1]. Doe C, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. | |
GSK269962A is a potent ROCK inhibitor with IC50s of 1.6 and 4 nM for recombinant human ROCK1 and ROCK2 respectively.
GSK269962A IC50 values of 1.6 nM toward recombinant human ROCK1. GSK269962A also exhibits more than 30-fold selectivity against a panel of serine/threonine kinases. GSK269962A induces vasorelaxation in preconstricted rat aorta with an IC50 of 35 nM. Both are highly potent toward human ROCK1 with IC50 of 1.6 nM for GSK269962A. On the other hand, GSK269962A has a significantly improved kinase selectivity profile with at least >30-fold selectivity against the panel of protein kinase tested[1].
Oral administration of GSK269965A (0.3, 1, and 3 mg/kg) induces a dose-dependent reduction in blood pressure in spontaneously hypertensive rat (SHR). The reduction of blood pressure is acute and substantial. The maximal effect on blood pressure is observed approximately 2 h after oral gavages for both compounds. Under a similar setting, oral administration of Y-27632 (10 and 30 mg/kg) also induced a dose-dependent decrease of blood pressure. For all three Rho kinase inhibitors, the reduction of blood pressure is accompanied by an acute, dose-dependent increase in heart rate, presumably due to the activation of baroreflex mechanism[1].
References:
[1]. Doe C, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.
| Cas No. | 850664-21-0 | SDF | |
| 别名 | N-[3-[[2-(4-氨基呋咱-3-基)-1-乙基-1H-咪唑并[4,5-C]吡啶-6-基]氧]苯基]-4-[[2-(4-吗啉基)乙基]氧]苯甲酰胺,GSK 269962 | ||
| 化学名 | N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(2-morpholin-4-ylethoxy)benzamide | ||
| Canonical SMILES | CCN1C2=CC(=NC=C2N=C1C3=NON=C3N)OC4=CC=CC(=C4)NC(=O)C5=CC=C(C=C5)OCCN6CCOCC6 | ||
| 分子式 | C29H30N8O5 | 分子量 | 570.6 |
| 溶解度 | DMF: 16 mg/ml,DMF:PBS(pH7.2) (1:2): 0.3 mg/ml,DMSO: 14 mg/ml | 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 | 1.7525 mL | 8.7627 mL | 17.5254 mL |
| 5 mM | 0.3505 mL | 1.7525 mL | 3.5051 mL |
| 10 mM | 0.1753 mL | 0.8763 mL | 1.7525 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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