Apatinib Mesylate

Apatinib Mesylate is a potent, orally bioavailable, ATP-competitive VEGFR-2 tyrosine kinase inhibitor with a cell-free IC₅₀ of 1nM^[1]. Apatinib Mesylate suppresses VEGFR-2 phosphorylation and downstream PLCγ1/ERK1/2, PI3K/AKT, and STAT3 signaling, thereby limiting cell proliferation, survival, migration, and angiogenesis^[1][2][4]. Apatinib Mesylate is used in research on tumor angiogenesis, solid-tumor growth and migration, leukemia biology, autophagy, and ABC-transporter-mediated multidrug resistance^{[2][3][4][5][6][7]}.

In vitro, Apatinib Mesylate inhibited VEGF-stimulated human umbilical vein endothelial cell proliferation over 72h with an IC₅₀ of 0.17μM, whereas the IC₅₀ against 20% fetal bovine serum-stimulated proliferation was 23.4μM^[1]. In SGC-7901 and BGC-823 human gastric cancer cells, Apatinib Mesylate (100, 500, and 1000nM; 24h) reduced proliferation and VEGF secretion; Apatinib Mesylate (500nM overnight; VEGF stimulation for 30min) reduced phosphorylation of VEGFR-2, PLCγ1, and ERK1/2, while MGC-803 cells with low pathway activity showed no significant proliferation response^[2]. In KHOS and MG63 human osteosarcoma cells, Apatinib Mesylate (10μM; 48h) increased apoptosis and autophagic markers, induced G0/G1 arrest, and reduced STAT3 and BCL-2 signaling^[3]. In Jurkat and Nalm6 human acute lymphoblastic leukemia cells, Apatinib Mesylate (0, 10, 20, and 40μM; 48h) dose-dependently reduced VEGFR-2, ERK, AKT, and STAT3 pathway activation^[4]. In human malignant peritoneal mesothelioma cells, Apatinib Mesylate (0, 12.5, 25, 50, and 100μM; 24, 48, and 72h) inhibited proliferation in concentration- and time-dependent manners, with IC₅₀ values of 46.34μM, 45.14μM, and 28.73μM at 24, 48, and 72h, respectively^[5].

In vivo, female nude mice bearing CNE-2 human nasopharyngeal carcinoma xenografts received Apatinib Mesylate (200mg/kg/day; intragastric gavage once daily for 7 days), which reduced the VEGFR-2-positive tumor-cell proportion from 92.83% to 54.50%, decreased CD31-defined microvessel density from 8.67 to 5.00, and inhibited tumor growth^[6]. NODscid-IL2Rg⁻/⁻ mice bearing Nalm6 human acute lymphoblastic leukemia xenografts received Apatinib Mesylate (100mg/kg/day; oral gavage once daily from Monday to Friday for 2 weeks), which reduced human CD45-positive leukemia cells in peripheral blood, bone marrow, and spleen and decreased spleen weight^[4]. In ABCB1-overexpressing KBv200 human cancer nude mouse xenograft model, Apatinib Mesylate (70mg/kg; oral administration every 3 days for four doses; 1h before paclitaxel) enhanced the antitumor activity of paclitaxel and produced 52.7% tumor-growth inhibition without apparent body-weight loss^[7].

References:

[1] 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;102(7):1374-1380. doi:10.1111/j.1349-7006.2011.01939.x.

[2] Lin Y, Zhai E, Liao B, Xu L, Zhang X, Peng S, et al. Autocrine VEGF signaling promotes cell proliferation through a PLC-dependent pathway and modulates Apatinib treatment efficacy in gastric cancer. Oncotarget. 2017;8(7):11990-12002. doi:10.18632/oncotarget.14467.

[3] Liu K, Ren T, Huang Y, Sun K, Bao X, Wang S, Zheng B, Guo W. Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma. Cell Death Dis. 2017;8:e3015. doi:10.1038/cddis.2017.422.

[4] Deng M, Zha J, Jiang Z, Jia X, Shi Y, Li P, et al. Apatinib exhibits anti-leukemia activity in preclinical models of acute lymphoblastic leukemia. J Transl Med. 2018;16:47. doi:10.1186/s12967-018-1421-y.

[5] Yang ZR, Chen ZG, Du XM, Li Y. Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo. Front Oncol. 2020;10:585079. doi:10.3389/fonc.2020.585079.

[6] Peng QX, Han YW, Zhang YL, Hu J, Fan J, Fu SZ, Xu S, Wan Q. Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma. Oncotarget. 2017;8:52813-52822. doi:10.18632/oncotarget.17264.

[7] Mi YJ, Liang YJ, Huang HB, Zhao HY, Wu CP, Wang F, et al. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010;70(20):7981-7991. doi:10.1158/0008-5472.CAN-10-0111.