| 生物活性 |
Regorafenib (BAY 73-4506) monohydrate is an orally active and potent multi-targeted receptortyrosine kinaseinhibitor, withIC50values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM forVEGFR1/2/3,PDGFRβ,Kit,RETandRaf-1, respectively. Regorafenib monohydrate shows very robust antitumor and antiangiogenic activity[1].
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| IC50& Target[1] |
Raf-1 2.5 nM (IC50) |
VEGFR2 4.2 nM (IC50) |
VEGFR1 13 nM (IC50) |
BRafV600E 19 nM (IC50) |
PDGFRβ 22 nM (IC50) |
Braf 28 nM (IC50) |
VEGFR3 46 nM (IC50) |
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体外研究
(In Vitro) |
Regorafenib monohydrate (0-10 μM, 96 h) shows anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells[1].
Regorafenib monohydrate (0-3000 nM, 30 min) inhibits the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, and inhibits FGFR and pERK1/2[1].
Regorafenib monohydrate causes a concentration-dependent decrease in Hep3B cell growth, with an IC50of 5 μM. Regorafenib subsequently increases the levels of phospho-c-Jun, a JNK target, but not total c-Jun in Hep3B cells[3].
Cell Proliferation Assay[1]
| Cell Line: |
GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells |
| Concentration: |
10 μM and 5 nM |
| Incubation Time: |
96 h |
| Result: |
Showed anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells, with IC50values of 45 ± 20, 34 ± 8, 401 ± 88, 560 ± 200, 900, 967 ± 287 nM. respectively. |
Western Blot Analysis[1]
| Cell Line: |
NIH-3T3/VEGFR2 cells, (CHO)-TIE2 cells, HAoSMCs cells, MCF-7 cells |
| Concentration: |
0, 10, 30, 100, 300, 1000, 3000 nM |
| Incubation Time: |
30 min |
| Result: |
Inhibited the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, with IC50values of 3, 31, and 90 nM, respectively, inhibited FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10, and showed inhibition of phosphorylated FGFR substrate 2 (pFRS2) and the downstream signaling kinase pERK1/2. |
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体内研究
(In Vivo) |
Regorafenib monohydrate (10 mg/kg, Orally, single dose or daily for 4 days) inhibits tumor vasculature and tumor growth in a rat GS9L glioblastoma model[1].
Regorafenib monohydrate (0-100 mg/kg, Orally, qd × 9) exhibits antitumorigenic and antiangiogenic effects in the Colo-205, MDA-MB-231 and 786-O model[1].
| Animal Model: |
Rat GS9L glioblastoma xenograft[1] |
| Dosage: |
10 mg/kg |
| Administration: |
Orally, single dose or daily for 4 days |
| Result: |
Inhibited tumor vasculature and tumor growth in a rat GS9L glioblastoma model. |
| Animal Model: |
Female athymic NCr nu/nu mice, Multiple xenograft models, including models derived from CRC (Colo-205), BC (MDA-MB-231) and RCC (786-O) tumors[1] |
| Dosage: |
0, 3, 10, 30, 100 mg/kg |
| Administration: |
Orally, qd × 9 |
| Result: |
Effectively inhibited growth of the Colo-205, MDA-MB-231 and 786-O model. Significantly reduces tumor MVA, effectively inhibited the RAF/MEK/ERK signaling cascade, and drastically inhibited tumor cell proliferation. |
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| Clinical Trial |
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| 分子量 |
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| 性状 |
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| Formula |
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| CAS 号 |
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| 中文名称 |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
| Powder |
-20°C |
3 years |
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4°C |
2 years |
| In solvent |
-80°C |
6 months |
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-20°C |
1 month |
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| 溶解性数据 |
In Vitro:
DMSO : 50 mg/mL(99.83 mM;Need ultrasonic)
配制储备液
| 1 mM |
1.9967 mL |
9.9834 mL |
19.9669 mL |
| 5 mM |
0.3993 mL |
1.9967 mL |
3.9934 mL |
| 10 mM |
0.1997 mL |
0.9983 mL |
1.9967 mL |
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请根据半岛bd体育手机客户端 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半岛bd体育手机客户端 失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶
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1.
请依序添加每种溶剂： 10% DMSO40%PEG3005%Tween-8045% saline
Solubility: ≥ 2.5 mg/mL (4.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.99 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
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2.
请依序添加每种溶剂： 10% DMSO90%corn oil
Solubility: ≥ 2.5 mg/mL (4.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.99 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
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以上所有助溶剂都可在本网站选购。
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