Apatinib Mesylate is a VEGFR2 inhibitor with IC50 of 1 nM and also can suppress the activities of Ret (IC50 = 13 nM),c-Kit (IC50 = 429 nM) and c-Src (IC50 = 530 nM).
Vascular endothelial growth factor (VEGF) regulates angiogenesis and endothelial cell function via binding to three membrane receptor tyrosine kinases: VEGFR‐1, VEGFR‐2, and VEGFR‐3. Apatinib Mesylate is a mesylate form of Apatinib. Apatinib is a selective inhibitor of VEGFR‐2 with an IC50 value of 1 nM. The kinase activities of Ret, c-Kit and c-Src tyrosine kinases could also be potently inhibited by apatinib with IC59 values of 0.013, 0.429 and 0.53 μM, respectively. In human umbilical vein endothelial cells (HUVEC), apatinib decreased VEGF‐stimulated activation of VEGFR‐2/KDR at a dose-dependent manner, and complete inhibition of VEGFR‐2/KDR phosphorylation was observed when 0.1 μM apatinib was applied. Apatinib at 0.01 – 10 μM also suppressed the activation of c‐kit and PDGFRβ in Mo7e and NIH‐3T3 cells. The proliferation of HUVEC induced by 20% FBS was inhibited by apatinib with an IC50 value of 23.4 μM, and the proliferation stimulated by 20 ng/mL VEGF was significantly blocked by apatinib with an IC50 value of 0.17 μM. Apatinib at 1 μM prevented HUVEC from forming the tubes and significantly inhibited FBS-triggered cell migration. Two-week oral administration of apatinib (100 and 200 mg/kg/day, once per day) significantly inhibited tumor growth in immunodeficient mice implanted with human tumor xenografts. In mice implanted with NCI‐H460 tumor, the antitumor effect of apatinib (150 mg/kg/day) alone was enhanced by the combination with docetaxel (12 mg/kg), showing 93% inhibition after two weeks of treatment[4].
作用机制
Apatinib is a small antiangiogenic molecule that specifically binds to the phosphorylation sites of VEGFR-2, inhibiting VEGF binding and subsequent VEGFR-2 autophosphorylation[5].
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