Takeda-6d

Takeda-6D (compound 6d) is an orally active and potent BRAF/VEGFR2 inhibitor, with IC50 values of 7.0 and 2.2 nM, respectively. Takeda-6D shows antiangiogenesis by suppressing the VEGFR2 pathway in 293/KDR and VEGF-stimulated HUVEC cells.Takeda-6D shows significant suppression of ERK1/2 phosphorylation. Takeda-6D shows antitumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> MAPK/ERK Pathway >> Raf

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR

Signaling Pathways >> Cell Cycle/DNA Damage >> PERK

VEGFR2:2.2 nM (IC50)

Braf:7.0 nM (IC50)

Takeda-6D (compound 6d) (10 mg/kg, Orally, once) shows sufficient oral bioavailability (F = 70.5%) in rats[1]. Takeda-6D (0-10 mg/kg, Orally, once) significantly decreases phosphorylation levels of ERK1/24 h after oral administration in an A375 (BRAFV600E mutant) human melanoma xenograft model in rats[1]. Takeda-6D (10 mg/kg, Orally, twice daily for 2 weeks) shows tumor regression with T/Cof −7.0% without severe toxicity, and this tumor regression should include the efficacy based on the antiangiogenesis potency and BRAF inhibitory activity[1].

[1]. Okaniwa M, et al. Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors. 1. Exploration of [5,6]-fused bicyclic scaffolds. J Med Chem. 2012 Apr 12;55(7):3452-78.