生物活性

• 靶点

  c-RET IC50:13nM

  VEGFR2 IC50:1nM

  c-Kit IC50:429nM

  Src IC50:530nM

• 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 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].

• 动物研究
  剂量	Mice: 0.2 mg/kg - 2 mg/kg[3] (p.o.), 50 mg/kg - 200 mg/kg[1] (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
  NCT03707028	Gastric Cancer ... more >> Gastroesophageal Junction Adenocarcinoma Collapse <<	Phase 1 Phase 2	Recruiting	August 2020	Korea, Republic of ... more >> Asan Medical Center Recruiting Seoul, Korea, Republic of, 05505 Contact: Jungran Lim    +82-2-3010-2219    junglim@amc.seoul.kr    Principal Investigator: Yoon-Koo Kang, MD, PhD          Sub-Investigator: Min-Hee Ryu, MD, PhD Collapse <<
  NCT03411967	Lung Cancer	Phase 2	Not yet recruiting	December 1, 2021	-
  NCT03396211	Cancer	Phase 1	Recruiting	December 22, 2019	United States, California ... more >> Sarcoma Oncology Research Center Recruiting Santa Monica, California, United States, 90403 Contact: Victoria Chua    310-552-9999    vchua@sarcomaoncology.com    Principal Investigator: Sant P. Chawla, M.D. Collapse <<

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• 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] Wang Y, Tang Z, et al. A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells. Onco Targets Ther. 2018 Nov 29;11:8529-8541.

  [4] 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.

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

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