Regorafenib (Hydrochloride)

835621-07-3

C21H16Cl2F4N4O3

DMSO : >= 5.6 mg/mL (10.78 mM)

Protein Tyrosine Kinase/RTK; MAPK/ERK Pathway; Protein Tyrosine Kinase/RTK; Autophagy; Protein Tyrosine Kinase/RTK

Regorafenib Hydrochloride is a multi-target inhibitor for VEGFR1/2/3, PDGFRbeta, Kit, RET and Raf-1 with IC₅₀s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM, respectively. IC50 & Target: IC50: 13 nM (VEGFR1), 4.2 nM (VEGFR2), 46 nM (VEGFR3), 22 nM (PDGFRbeta), 7 nM (Kit), 1.5 nM (RET), 2.5 nM (Raf-1) In Vitro: Regorafenib potently inhibits VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with an IC₅₀ of 3 nM. In HAoSMCs, regorafenib inhibits PDGFR-beta 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^[1]. Regorafenib causes a concentration-dependent decrease in Hep3B cell growth, having an IC₅₀ of 5 uM. Regorafenib subsequently increases the levels of phospho-c-Jun, a JNK target, but not total c-Jun in Hep3B cells^[3]. In Vivo: 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^[1].