AS#: 1218779-75-9 (Apatinib mesylate salt); 811803-05-1 (Apatinib free base).
Description: Apatinib mesylate is an orally bioavailable, small-molecule receptor tyrosine kinase inhibitor with potential antiangiogenic and antineoplastic activities. Apatinib selectively binds to and inhibits vascular endothelial growth factor receptor 2, which may inhibit VEGF-stimulated endothelial cell migration and proliferation and decrease tumor microvessel density. In addition, this agent mildly inhibits c-Kit and c-SRC tyrosine kinases. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
Synonym: YN-968D1; YN 968D1; YN968D1; Apatinib.
IUPAC/Chemical Name: N-(4-(1-cyanocyclopentyl)phenyl)-2-((4-methylpyridin-3-yl)amino)nicotinamide methanesulfonate
Name: Apatinib mesylate
CAS#: 1218779-75-9 (Apatinib mesylate salt); 811803-05-1 (Apatinib free base).
Chemical Formula: C25H27N5O4S
Molecular Weight: 493.58
Elemental Analysis: C, 60.83; H, 5.51; N, 14.19; O, 12.97; S, 6.50
Apatinib, also known as YN968D1, is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR2, also known as KDR). It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis in cancer cells; specifically apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. This agent also mildly inhibits c-Kit and c-SRC tyrosine kinases.
History of Apatinib: Apatinib was first synthesized by Advenchen Laboratories in California, USA and is being developed by Jiangsu Hengrui Medicine (China), LSK BioPartners (US) and Bukwang Pharmaceutical Company (Korea). It is an investigational cancer drug currently undergoing clinical trials as a potential targeted treatment for metastatic gastric carcinoma, metastatic breast cancer and advanced hepatocellular carcinoma. (source: http://en.wikipedia.org/wiki/Apatinib).
Development status of Apatinib: There is a Phase II/III study recruiting patients in China to determine whether apatinib can improve progression free survival compared with placebo in patients with metastatic gastric carcinoma who have failed two lines of chemotherapy (September, 2009). As of November, 2010, two additional Phase 2 clinical studies have been initiated for apatinib in metastatic triple-negative breast cancer patients and advanced hepatocellular carcinoma. On March 7, 2011, Bukwang announced that it filed an IND to the Korean FDA to begin Human clinical studies of Apatinib in Phase 2. (source: http://en.wikipedia.org/wiki/Apatinib).
1: Tong XZ, Wang F, Liang S, Zhang X, He JH, Chen XG, Liang YJ, Mi YJ, To KK, Fu LW. Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells. Biochem Pharmacol. 2012 Mar 1;83(5):586-97. Epub 2011 Dec 16. PubMed PMID: 22212563.
2: Liang S, Tong XZ, Fu LW. [Inhibitory effect of apatinib on HL-60 cell proliferation and its mechanism]. Nan Fang Yi Ke Da Xue Xue Bao. 2011 May;31(5):871-4. Chinese. PubMed PMID: 21602146.
3: Tian S, Quan H, Xie C, Guo H, LÃ¼ 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. doi: 10.1111/j.1349-7006.2011.01939.x. Epub 2011 May 9. PubMed PMID: 21443688.
4: Li J, Zhao X, Chen L, Guo H, Lv F, Jia K, Yv K, Wang F, Li C, Qian J, Zheng C, Zuo Y. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010 Oct 5;10:529. PubMed PMID: 20923544; PubMed Central PMCID: PMC2984425.
5: Mi YJ, Liang YJ, Huang HB, Zhao HY, Wu CP, Wang F, Tao LY, Zhang CZ, Dai CL, Tiwari AK, Ma XX, To KK, Ambudkar SV, Chen ZS, Fu LW. 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. Epub 2010 Sep 28. PubMed PMID: 20876799; PubMed Central PMCID: PMC2969180.