Regorafenib (monohydrate)

Regorafenib (BAY 73-4506) monohydrate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC₅₀ values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib monohydrate shows very robust antitumor and antiangiogenic activity^[1]. IC50 & Target:IC50: 1.5 ± 0.7 nM (RET), 2.5 ± 0.6 nM (Raf-1), 4.2 ± 1.6 nM (VEGFR2), 7 ± 2 nM (Kit), 13 ± 0.4 nM (VEGFR1), 19 ± 6 nM (B-RAF V600E), 22 ± 3 nM (PDGFRβ), 28 ± 10 nM (B-RAF), 46 ± 10 nM (VEGFR3), 202 ± 18 nM (FGFR1), 311 ± 46 nM (TIE2)^[1] 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 IC₅₀ of 5 μM. Regorafenib subsequently increases the levels of phospho-c-Jun, a JNK target, but not total c-Jun in Hep3B cells^[3]. 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].