KG5

KG5 is an orally active dual PDGFRβ and B-Raf allosteric inhibitor. KG5 also inhibits Flt3, KIT and c-Raf. KG5 has anticancer, antiangiogenic activities^[1]. In Vitro: KG5 (Compound 6) inhibits vascular smooth muscle cells (VSMCs) and endothelial cells viability with EC₅₀ values of 0.59 μM and 0.54 μM, respectively^[1].
Compound 6 selectively blocks S338 phosphorylation, yet does not influence S259^[1].
KG5 (Compound 6) inhibits only PDGFRα and β with K_ds of 300 and 520 nM, respectively, and Flt3 and KIT at 52 and 170 nM, respectively^[1].
KG5 (Compound 6; 5 μM) inhibits phosphorylation of MEK and ERK in endothelial cells stimulated with bFGF or VEGF^[1]. In Vivo: KG5 (Compound 6; 100 mg/kg; oral administration; daily; for 26 days) treatment prevents tumor growth in an orthotopic renal cell carcinoma model^[1].
KG5 (Compound 6; 50 mg/kg; i.p.; twice daily) treatment completely blocks angiogenesis relative to vehicle control in mice (injected with Matrigel containing bFGF). Pharmacokinetic analysis of the dose and formulation of KG5 used indicated a C_max of 3.6 μg/mL, T_1/2 of 11.5 h, and an area under the concentration time curve (AUC_0-12h) of 14.7 μg?h/mL^[1].
KG5 (Compound 6; 1 μM) disrupts a late step in angiogenesis during zebrafish embryogenesis^[1].