KG5 is an orally active dual inhibitor of PDGFRβ and B-Raf through allosteric mechanisms. Additionally, KG5 exhibits inhibitory activity against Flt3, KIT, and c-Raf. The compound possesses anticancer and antiangiogenic properties [1].
体内研究
In vivo treatment with KG5 at a dose of 100 mg/kg via oral administration daily for 26 days effectively prevents tumor growth in an orthotopic renal cell carcinoma model [1].
Furthermore, treatment with KG5 at a dose of 50 mg/kg intraperitoneally twice daily completely suppresses angiogenesis compared to vehicle control in mice injected with Matrigel containing bFGF. Pharmacokinetic analysis reveals a Cmax of 3.6 μg/mL, a half-life (T1/2) of 11.5 h, and an area under the concentration-time curve (AUC0-12h) of 14.7 μg•h/mL for the dose and formulation of KG5 utilized [1].
KG5 at a concentration of 1 μM disrupts a late step in angiogenesis during zebrafish embryogenesis [1].
体外研究
KG5 effectively inhibits the viability of vascular smooth muscle cells (VSMCs) and endothelial cells, with EC50 values of 0.59 μM and 0.54 μM, respectively [1].
KG5 selectively blocks S338 phosphorylation, yet does not influence S259[1].
KG5 demonstrates inhibition of PDGFRα and β with dissociation constants (Kds) of 300 and 520 nM, respectively, as well as Flt3 and KIT at 52 and 170 nM, respectively [1].
Exposure of KG5 at a concentration of 5 μM leads to the inhibition of MEK and ERK phosphorylation in endothelial cells stimulated with bFGF or VEGF [1].
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