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  • Regorafenib
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Regorafenib

A multi-kinase inhibitor

原价
¥412-1625
价格
330-1300
Regorafenib的二维码

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  • 货号: ajci4464
  • CAS: 755037-03-7
  • 别名: 瑞戈非尼; BAY 73-4506
  • 分子式: C21H15ClF4N4O3
  • 分子量: 482.82
  • 纯度: >98%
  • 溶解度: ≥ 25.0415mg/mL in DMSO, ≥ 6.25 mg/mL in EtOH with ultrasonic,insoluble in Water
  • 储存: Desiccate at -20°C
  • 库存: 现货

Background

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].

参考文献:
[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.

Protocol

Cell experiment: [1]

Cell lines

PLC/PRF/5 cells

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.

Reaction Conditions

1 μM, 72 hours for migration assay 5 μM, 24 hours for invasion assay

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]

Animal models

Female athymic NCr nu/nu mice injected with Colo-205, MDA-MB-231 or 786-O xenografts

Dosage form

Oral administration; 100, 30, 10, and 3 mg/kg

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.

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.

参考文献:

[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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