Background:

SU6656 is a small-molecule, potent and selective inhibitor of Src tyrosine kinases.

Src (proto-oncogene tyrosine-protein kinase) is a non-receptor protein tyrosine kinase family including 9 members and promotes survival, angiogenesis, and proliferation and invasion pathways.

In NIH 3T3 cell, SU6656 inhibits PDGF-/Src-driven mitogenesis and PDGF-stimulated c-Myc induction. [1] In UT-7/TPO, SU6656 cause ceased cell division but DNA continues accumulating by endomitosis. It also increased CD41 and CD61 expression on the cell surface in. [2] SU6656 in combination with radiation decrease clonogenic survival of endothelial cells. Src family kinase inhibition by SU6656 attenuated radiation-induced Akt phosphorylation and increased radiation-induced apoptosis and vascular endothelium destruction. [3]

In vivo, SU6656 administered prior to irradiation significantly promotes radiation-induced destruction of blood vessels within the tumor windows. It also facilitates tumor growth delay when administered during fractionated irradiation. [3]

参考文献:
1.  Blake RA, Broome MA, Liu X et al. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol. 2000 Dec;20(23):9018-27.
2.  Lannutti BJ, Blake N, Gandhi MJ et al. Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656. Blood. 2005 May 15;105(10):3875-8.
3.  Cuneo KC, Geng L, Tan J et al. SRC family kinase inhibitor SU6656 enhances antiangiogenic effect of irradiation. Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1197-203.