生物活性

• 靶点	VEGFR2 IC50:1nM

• 描述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 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^[3].
• 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^[4].

• 动物研究
  剂量	Mice: 37.5 mg/kg - 150 mg/kg[3] (p.o.); 100 mg/kg - 300 mg/kg[4] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03389087	Small Cell Lung Cancer	Phase 2	Recruiting	November 2019	China, Henan ... more >> Henan Cancer Hospital Recruiting Zhengzhou, Henan, China, 450008 Contact: Qiming Wang    13783590691    qimingwang1006@126.com Collapse <<
  NCT03334591	Two Different Treatment Method... more >>s Collapse <<	Phase 2	Recruiting	December 1, 2019	China, Anhui ... more >> Anhui Provincial Cancer Hospital Recruiting Hefei, Anhui, China, 230000 Contact: yifu he, doctor    0551-65327666    834638033@qq.com Collapse <<
  NCT03359018	Progression-free Survival ... more >> Overall Survival Clinical Benefit Rate Toxicity Collapse <<	Phase 2	Active, not recruiting	March 1, 2020	China ... more >> Musculoskeletal Tumor Center of Peking University People's Hospital Beijing, China, 100044 Peking University Shougang Hospital Beijing, China, 100144 Collapse <<

• 更多
• 参考文献

• [1] Tian S, Quan H, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.

  [2] Mi YJ, Liang YJ, et al. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010 Oct 15;70(20):7981-91.

  [3] Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y, Li J, Lou L. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.

  [4] Zhang H. Apatinib for molecular targeted therapy in tumor. Drug Des Devel Ther. 2015 Nov 13;9:6075-81.