Regorafenib
(Synonyms: 瑞戈非尼; BAY 73-4506) 目录号 : GC10111
A multi-kinase inhibitor
Cas No.:755037-03-7
Sample solution is provided at 25 µL, 10mM.
Regorafenib (BAY 73-4506) is a novel and orally active multikinase inhibitor of receptor tyrosine kinases VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET, Raf-1, B-RAF and B-RAFV600E with IC50 values of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM, 2.5 nM, 28 nM and 19 nM [1].
VEGFR1/2/3 are vascular endothelial growth factor receptor plays an important role in the formation of normal and tumor vasculature. platelet-derived growth factor receptor-β (PDGFRβ) is a receptor for the platelet-derived growth factor family. Kit, RET and B-RAF are both receptor tyrosine kinases that encoded by proto-oncogenes [1].
Regorafenib (BAY 73-4506) is a novel and orally active receptor tyrosine kinases inhibitor. In NIH-3T3/VEGFR2 cells, regorafenib potently inhibited VEGFR2 autophosphorylation with IC50 value of 3 nM. Regorafenib also inhibited TIE2 and PDGFR-β autophosphorylation with IC50 values of 31 and 90 nM. Regorafenib potently inhibited KITK642E and RETC634W with IC50 values of ~20 and ~10 nM, respectively. In addition, regorafenib inhibited the proliferation of VEGF165-stimulated HUVECs with IC50 value of ~3 nM [1].
In GS9L glioblastoma xenografted rat model, regorafenib administered orally at 10 mg/kg significantly reduced the extravasation of Gadomer in the vasculature. In various preclinical human xenograft mice models, regorafenib exhibited potent dose-dependent tumor growth inhibition (TGI) [1]. In murine metastatic colorectal cancer (CRC) liver metastasis model, regorafenib significantly delayed disease progression by inhibiting the growth of liver metastases and preventing the formation of new metastases in other organs [2].
References:
[1]. Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer, 2011, 129(1): 245-255.
[2]. Schmieder R, Hoffmann J, Becker M, et al. Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical models of colorectal cancer. Int J Cancer, 2014, 135(6): 1487-1496.
| Cell experiment: [1] | |
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Cell lines |
PLC/PRF/5 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 72 hours for migration assay 5 μM, 24 hours for invasion assay |
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Applications |
For the migration assay, PLC/PRF/5 cells were treated with the drugs and microscopically analyzed at the time of the scratch (T0) and after 48 and 72 hours. For the invasion assay, invading PLC/PRF/5 cells were treated with different drug concentrations (0.5, 1, 2.5 and 5 μM). Invasion was calculated as a percentage of the invading drug-treated cells compared to drug-untreated control cells. Regorafenib inhibited HCC cell migration in both AFP-positive and AFP-negative cells at the same low concentration range as inhibited AFP levels. Similar results were found in a cell invasion assay, at almost identical drug concentrations. |
| Animal experiment: [2] | |
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Animal models |
Female athymic NCr nu/nu mice injected with Colo-205, MDA-MB-231 or 786-O xenografts |
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Dosage form |
Oral administration; 100, 30, 10, and 3 mg/kg |
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Applications |
Regorafenib dosed qd orally inhibited tumor growth in a dose-dependent manner in multiple xenograft models, including models derived from CRC (Colo-205), BC (MDA-MB-231) and RCC (786-O) tumors. Regorafenib effectively inhibited growth of the Colo-205 xenografts in the dose range of 10-100 mg/kg, reaching a TGI of about 75% at day 14 at the 10 mg/kg dose. A slow regrowth was observed at all doses when treatment was terminated after 9 days. In the MDA-MB-231 model, regorafenib was highly efficacious at a dose as low as 3 mg/kg, resulting in a significant TGI of 81%, which increased to ~ 93% at doses of 10 and 30 mg/kg, where tumor stasis was reached. Regorafenib also very efficiently inhibited the growth of the 786-O RCC model. TGI >90% was observed at the end of a 21-day dosing period with regorafenib 10 and 30 mg/kg. |
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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] Carr B I, D'Alessandro R, Refolo M G, et al. Effects of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro. Journal of cellular physiology, 2013, 228(6): 1344-1350. [2] Wilhelm S M, Dumas J, Adnane L, et al. Regorafenib (BAY 73‐4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. International Journal of Cancer, 2011, 129(1): 245-255. |
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| Cas No. | 755037-03-7 | SDF | |
| 别名 | 瑞戈非尼; BAY 73-4506 | ||
| 化学名 | 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide | ||
| Canonical SMILES | CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F | ||
| 分子式 | C21H15ClF4N4O3 | 分子量 | 482.82 |
| 溶解度 | ≥ 25.0415mg/mL in DMSO, ≥ 6.25 mg/mL in EtOH with ultrasonic,insoluble in Water | 储存条件 | Desiccate 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 | 2.0712 mL | 10.3558 mL | 20.7117 mL |
| 5 mM | 0.4142 mL | 2.0712 mL | 4.1423 mL |
| 10 mM | 0.2071 mL | 1.0356 mL | 2.0712 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet