Regorafenib (BAY 73-4506) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively.
IC50&Target
VEGFR1
13 nM (IC50)
VEGFR2
4.2 nM (IC50)
VEGFR3
46 nM (IC50)
PDGFRβ
22 nM (IC50)
Raf-1
2.5 nM (IC50)
Braf
28 nM (IC50)
BRaf
19 nM (IC50)
体外研究
Regorafenib potently inhibits VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with an IC50 of 3 nM. In HAoSMCs, regorafenib inhibits PDGFR-β autophosphorylation after stimulation with PDGF-BB, with an IC50 of 90 nM. Regorafenib inhibits the proliferation of VEGF165-stimulated HUVECs, with an IC50 of 3 nM. Regorafenib causes a concentration-dependent decrease in Hep3B cell growth, having an IC50 of 5 μM. Regorafenib subsequently increases the levels of phospho-c-Jun, a JNK target, but not total c-Jun in Hep3B cells.
体内研究
Regorafenib effectively inhibits growth of the Colo-205 xenografts in the dose range of 10-100 mg/kg reaching a TGI of 75% at day 14 at the 10 mg/kg dose. In the MDA-MB-231 model, regorafenib is highly efficacious at a dose as low as 3 mg/kg, resulting in a significant TGI of 81%, which increases to 93% at doses of 10 and 30 mg/kg, where tumor stasis is reached.
分子式
C21H15ClF4N4O3
分子量
482.82
CAS号
755037-03-7
中文名称
瑞戈非尼;瑞格非尼;瑞格菲尼
运输条件
Room temperature in continental US; may vary elsewhere.