生物活性

• 靶点

  PDGFRβ Ki:5nM

  VEGFR2 Ki:6nM

• 描述Many of the processes involved in tumor growth, progression, and metastasis are mediated by ligand-receptor interactions involving RTKs (receptor tyrosine kinases) and downstream signaling molecules. Because of the demonstrated importance of RTKs in the control of many cellular processes (particularly proliferation) and the role of aberrant RTK signaling in cancer, RTKs have emerged as important targets for the development of anticancer therapies. Toceranib Phosphate is the phosphate form of Toceranib. Toceranib, a small molecule with an indolinone chemical structure, is a selective inhibitor of the tyrosine kinase activity of several members of the split kinase RTK family, including Flk-1/KDR, PDGFR, and Kit. In vitro, toceranib exerted a potent antiproliferative effect on endothelial cells. Additionally, toceranib treatment could induce cell cycle arrest and subsequent apoptosis in tumor cell lines expressing activating mutations in split kinase RTKs. In mouse xenograft models, oral administration of toceranib affected the growth of multiple tumor cell lines originating from a variety of tissues, leading to either tumor regression or tumor growth inhibition. On the basis of preclinical work in rodent models, the therapeutic range of toceranib for target inhibition was considered to be 50–100 ng/ml for 12 h of a 24-h dosing period^[3].