| 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]. |
| 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -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 |
*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℃, 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 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% 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。 2. 请依序添加每种溶剂： 10% DMSO 90%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。 *以上所有助溶剂都可在本网站选购。
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