KKL 顾客使用本产品发表的 2 篇科研文献

ON123300, a strong and brain-penetrant multi-kinase inhibitor, inhibits CDK4 (IC₅₀=3.9 nM), Ark5 (IC₅₀=5 nM), PDGFRβ (IC₅₀=26 nM), FGFR1 (IC₅₀=26 nM), RET (IC₅₀=9.2 nM), and FYN (IC₅₀=11 nM). Single agent ON123300 causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors. ON123300 inhibits CDK6 with an IC₅₀ of 9.82 nM.

ON123300 inhibits U87 glioma cell proliferation with an IC₅₀ of 3.4±0.1 μM. ON123300 (1 and 10 μM) inhibits cell proliferation in a panel of 11 glioma models including a patient-derived model (GBM10).
ON123300 (6.3 μM; 1 h) reduces phosphorylation of Akt and its downstream signaling components, P70S6K, 40S rpS6 and Rb S780, yet ON123300 induces Erk activation in U87 cells; both in a dose- and time-dependent manner. ON123300 inhibits PI3Kδ with the IC₅₀ of 144nM.

ON123300 decreases p-Akt expression and increases p-Erk activity in brain tumors upon administration at both IV doses of 5 mg/kg and 25 mg/kg in U87 brain tumor-bearing mouse. The half-life (T_1/2) is 1.5 h for 5 mg/kg and 25 mg/kg in plasma.

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