Defactinib hydrochloride
(Synonyms: VS-6063 hydrochloride; PF 04554878 hydrochloride) 目录号 : GC35827
A FAK inhibitor
Cas No.:1073160-26-5
Sample solution is provided at 25 µL, 10mM.
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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a vital role in many oncogenic pathways.1,2 Defactinib is a dose-dependent inhibitor of FAK, with maximal inhibition of FAK autophosphorylation in cells achieved at 10 ?M.3 It is less effective against the related kinase PYK2. Defactinib restores the chemosensitivity of taxane-resistant cells to paclitaxel , although it is not cytotoxic alone.3 Defactinib decreases YB-1 phosphorylation and nuclear accumulation in an Akt-dependent manner. It is orally bioavailable, inhibiting FAK and augmenting paclitaxel action in suppressing the growth and number of ovarian cancer cell tumors in mice.3
1.Schwock, J., Dhani, N., and Hedley, D.W.Targeting focal adhesion kinase signaling in tumor growth and metastasisExpert Opin. Ther. Targets14(1)77-94(2010) 2.Lee, B.Y., Timpson, P., Horvath, L.G., et al.FAK signaling in human cancer as a target for therapeuticsPharmacol. Ther.146132-149(2015) 3.Kang, Y., Hu, W., Ivan, C., et al.Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancerJNCI105(19)1485-1495(2013)
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Animal experiment: |
Mice[1] To determine the antitumor effects of Defactinib, SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells are injected intraperitoneally. One week after tumor cell injection, mice are randomly assigned to 4 groups of 10 mice (control, PTX alone, Defactinib alone, and PTX with Defactinib); treatment is initiated at 3-4 weeks following injection. PTX at 2 mg/kg (SKOV3ip1 and SKOV3-TR) or 2.5 mg/kg (HeyA8 and HeyA8-MDR) is given intraperitoneally weekly; Defactinib at 25 mg/kg is given orally twice every day. Control mice received HBSS intraperitoneally once a week and vehicle orally twice every day. Mice are monitored daily for adverse effects of therapy and are killed on day 35 (SKOV3ip1 or SKOV3-TR), day 28 (HeyA8 or HeyA8-MDR), or when any of the mice seemed moribund. Total body weight, tumor incidence and mass, and the number of tumor nodules are recorded. Tumors are either fixed in formalin or embedded in paraffin or snap frozen in optimal cutting temperature (OCT) compound in liquid nitrogen. |
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References: [1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. |
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| Cas No. | 1073160-26-5 | SDF | |
| 别名 | VS-6063 hydrochloride; PF 04554878 hydrochloride | ||
| Canonical SMILES | O=C(NC)C1=CC=C(NC2=NC=C(C(F)(F)F)C(NCC3=NC=CN=C3N(C)S(=O)(C)=O)=N2)C=C1.[H]Cl | ||
| 分子式 | C20H22ClF3N8O3S | 分子量 | 546.95 |
| 溶解度 | DMSO: 30 mg/mL (54.85 mM); Water: < 0.1 mg/mL (insoluble) | 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 | 1.8283 mL | 9.1416 mL | 18.2832 mL |
| 5 mM | 0.3657 mL | 1.8283 mL | 3.6566 mL |
| 10 mM | 0.1828 mL | 0.9142 mL | 1.8283 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet