| 生物活性 | Regorafenib (BAY 73-4506) mesylate 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 mesylate shows very robust antitumor and antiangiogenic activity[1]. |
体外研究
(In Vitro) | Regorafenib mesylate (0-10 μM, 96 h) shows anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells[1].
Regorafenib mesylate (0-3000 nM, 30 min) inhibits the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, and inhibits FGFR and pERK1/2[1].
Regorafenib mesylate 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[2].
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 mesylate (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 mesylate (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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