Background:

ZM 306416 is a selective inhibitor of VEGFR with IC50 value of 0.67μM [1]. It is also reported that ZM 306416 inhibits EGFR with IC50 value less than 10 nM [2].

Vascular endothelial growth factor receptor (VEGFR) is a key element of the extracellular matrix(ECM) and plays an important role in angiogenesis cooperating with its ligand VEGF. Several studies have demonstrated that VEGFRs expressed in liquid and solid tumor cells, such as NSCLC, melanoma, prostate cancer, leukemia, mesothelioma, and breast cancer and are being regarded as a promising target in clinical [3].

ZM 306416 is a potent VEGFR inhibitor and has a different selectivity with other reported VEGFR inhibitors. Using A549-EGFRB cells for EGFRB assay revealed that ZM 306416 exhibited inhibitory activity on VEGFR with IC50 value of 670 nM [1]. When tested with human thyroid follicular cells, ZM 306416 treatment exhibited function on reducing VEGFR2 phosphorylation and inhibiting endogenous, steady-state levels of p42/44 MAPK phosphorylation [4].

参考文献:
1.  Antczak, C., et al., A high-content biosensor-based screen identifies cell-permeable activators and inhibitors of EGFR function: implications in drug discovery. J Biomol Screen, 2012. 17(7): p. 885-99.
2.  Choi KJ, Baik IH, Ye SK et al. Molecular Targeted Therapy for Hepatocellular Carcinoma: Present Status and Future Directions. Biol Pharm Bull. 2015;38(7):986-91.
3.  Choi, K.J., et al., Molecular Targeted Therapy for Hepatocellular Carcinoma: Present Status and Future Directions. Biol Pharm Bull, 2015. 38(7): p. 986-91.
4.  Susarla, R., J.C. Watkinson, and M.C. Eggo, Regulation of human thyroid follicular cell function by inhibition of vascular endothelial growth factor receptor signalling. Mol Cell Endocrinol, 2012. 351(2): p. 199-207.