GW441756
目录号 : GC14123
A potent inhibitor of TrkA
Cas No.:504433-23-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
human muscle sarcoma cancer cell line HTB114 |
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Preparation method |
The solubility of this compound in DMSO is >13.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
IC50 = 2nM |
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Applications |
In human muscle sarcoma cancer cell line HTB114, GW441756 dose-dependently decreased neoplastic proliferation and significantly increased apoptosis in a dose-dependent way. GW441756 also increased the level of caspase-3, which then led to apoptosis. |
| Animal experiment [2]: | |
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Animal models |
Alzheimer’s disease (AD) mouse model, PDAPP (J20) mice |
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Dosage form |
10 mg/kg/day (subcutaneous injection, Sub-Q); 5 days |
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Application |
In Alzheimer’s disease (AD) mouse model, PDAPP (J20) mice, GW441756 at 10 mg/kg increased the level of sAβPPα and increased the sAβPPα to Aβ42 ratio to 1.85 times over control. At this dose, GW441756 gave measurable brain levels with a maximum brain concentration (Cmax, 1 h) of ~1×IC50 (50 nM). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Montagnoli C, Pistilli A, Stabile A M, et al. Anti-proliferative effects of GW441756, a novel inhibitor of NGFreceptor tyrosine kinase a (TRKA), in human sarcoma. Italian Journal of Anatomy and Embryology, 2010, 115(1/2): 117. [2]. Zhang Q#1, Descamps O#1, Hart MJ1, et al. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. | |
GW441756 is an inhibitor of TrkA kinase and LRRK2 with IC50 value of 320nM and 2nM, respectively [1].
The activity of TrkA kinase can affect its downstream signaling and involves in many biological processes including proliferation, differentiation and apoptosis. Thereby the inhibitor of TrkA is developed for the treatment of cancers. GW441756 belongs to the oxindole series and is found to be a potent inhibitor of TrkA. It is also selective against TrkA. The IC50 values of it for cRaf1 and CDK2 are above 12μM and 7μM, respectively. In human muscle sarcoma cancer cell line HTB114, treatment of GW441756 dose-dependently suppresses neoplastic proliferation and induces apoptosis [1, 2].
In addition, GW441756 is also found to be an LRRK2 inhibitor. It inhibits the Ser935 phosphorylation of LRRK2 in cellular TR-FRET assay with IC50 value of 2.2μM. It shows no significant cytotoxicity with IC50 value of >20μM [3].
References:
[1] Wood E R, Kuyper L, Petrov K G, et al. Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorganic & medicinal chemistry letters, 2004, 14(4): 953-957.
[2] Montagnoli C, Pistilli A, Stabile A M, et al. Anti-proliferative effects of GW441756, a novel inhibitor of NGFreceptor tyrosine kinase a (TRKA), in human sarcoma. Italian Journal of Anatomy and Embryology, 2010, 115(1/2): 117.
[3] Hermanson S B, Carlson C B, Riddle S M, et al. Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 Ser935 phosphorylation. PloS one, 2012, 7(8): e43580.
| Cas No. | 504433-23-2 | SDF | |
| 化学名 | (3Z)-3-[(1-methylindol-3-yl)methylidene]-1H-pyrrolo[3,2-b]pyridin-2-one | ||
| Canonical SMILES | CN1C=C(C2=CC=CC=C21)C=C3C4=C(C=CC=N4)NC3=O | ||
| 分子式 | C17H13N3O | 分子量 | 275.3 |
| 溶解度 | ≥ 13.75mg/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 | 3.6324 mL | 18.162 mL | 36.324 mL |
| 5 mM | 0.7265 mL | 3.6324 mL | 7.2648 mL |
| 10 mM | 0.3632 mL | 1.8162 mL | 3.6324 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。