CID 755673
目录号 : GC13589
An inhibitor of protein kinase D
Cas No.:521937-07-5
Sample solution is provided at 25 µL, 10mM.
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IC50: Selective protein kinase D (PKD) antagonist with the IC50 of 0.182, 0.280, 0.227, >10, 15.3, 20.3, 40.5 and >50 μM for PKD1, PKD2, PKD3, PKC, CAK, PLK1, CAMKIIα and Akt respectively.
CID755673, benzoxoloazepinolone, is the first identified cell-active small molecule PKD antagonist. It inhibits the activity of PKD1 with an IC50 of 182 nM and demonstrates highest selectivity to PKD1 when compared with AKT, PLK1, CAK, CAMKIIα, PKD2 and PKD3. Moreover, it was not competitive with ATP for enzyme inhibition. [1]
In vitro: In cell based assays, CID755673 dose-dependently suppressed PKD1 activation induced by phorbol ester endogenous in LNCaP cells. It was also reported to reverse biological actions of PKD1 including class IIa histone deacetylase 5 nuclear exclusion, vesicular stomatitis, virus glycoprotein delivery from the Golgi to the plasma membrane as well as the ilimaquinone-induced Golgi fragmentation. Moreover, CID755673 suppressed prostate cancer cell proliferation, cell migration, and invasion. [1]
In vivo: Experimental models of acute pancreatitis were developed to study the effect of CID755673 on acute pancreatitis in vivo. Results demonstrated that this compound suppressed PKD1/2 and therefore significantly offset necrosis and severity of pancreatitis. [2]
Clinical trial: So far, no clinical trial has been conducted.
References:
[1]Sharlow ER, Giridhar KV, LaValle CR, Chen J, Leimgruber S, Barrett R, Altamirano KB, Wipf P, Lazo JS and Wang QJ. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem. 2008 Nov. 283(48): 3351246.
[2]Yuan JZ, Liu YN, Tan TY, Guha S, Gukovsky I, Gukovskaya A and Pandol SJ. Protein kinase D regulates cell death pathways in experimental pancreatitis. Front Physiol. 2012 Mar. 3: DOI: 10.3389/fphys.2012.00060.
Kinase experiment: | The radiometric kinase assay is carried out by coincubating 0.5 μCi of [γ-32P]ATP, 20 μM ATP, 50 ng of purified recombinant human PKD (PKD1, PKD2, and PKD3) or CAMKIIα proteins, and 2.5 μg of Syntide-2 in 50 μL of kinase buffer that contains 50 mM Tris-HCl, pH 7.5, 4 mM MgCl2, 10 mM β-mercaptoethanol. The reaction is carried out under conditions that the initial rate is within the linear kinetic range[1]. |
Cell experiment: | The wound-induced migration is triggered by scraping the cells with a plastic pipette tip, and the wound is imaged immediately. The DU145 cells are then are treated with or without CID755673 at different concentrations. The wound is imaged immediately (0 h) and at different intervals with an inverted phase-contrast microscope with a ×10 objective. At the end of the assay, cells are fixed with methanol and stained with crystal violet for a final image[1]. |
Animal experiment: | Mice: For acute inhibitor studies, C57BL6 mice are administered a single dose of vehicle (5% DMSO in PBS, pH 7.4), or the selective PKD inhibitor CID755673 at 1 or 10mg/kg body weight. Mice are killed one or four hr later and heart collected for later analysis. For chronic inhibitor experiments, 8-week old db/db mice receives vehicle or CID755673 at 1 or 10mg/kg bodyweight for 16 days, by daily intraperitoneal (i.p.) injection[2]. |
References: [1]. Sharlow ER, et al. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem. 2008 Nov 28;283(48):33516-26. | |
| Cas No. | 521937-07-5 | SDF | |
| 化学名 | 7-hydroxy-2,3,4,5-tetrahydro-[1]benzofuro[2,3-c]azepin-1-one | ||
| Canonical SMILES | C1CC2=C(C(=O)NC1)OC3=C2C=C(C=C3)O | ||
| 分子式 | C12H11NO3 | 分子量 | 217.22 |
| 溶解度 | ≥ 5.55mg/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 | 4.6036 mL | 23.0181 mL | 46.0363 mL |
| 5 mM | 0.9207 mL | 4.6036 mL | 9.2073 mL |
| 10 mM | 0.4604 mL | 2.3018 mL | 4.6036 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%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet