Uses
A synthetic, orally bioavailable small molecule and non-ATP competitive Src tyrosine kinase inhibitor with an IC50 of average 72 nM.
Biological Activity
kx2-391 is a highly selective inhibitor of src kinase with ic50 value of 20nm [1].kx2-391 is a non-atp competitive inhibitor of src. it is the first inhibitor that targets src kinase within the substrate binding site. kx2-391 inhibits src catalyzed trans-phosphorylation of fak, shc, paxillin as well as src kinase autophosphorylation. kx2-391 has no effects on pdgfr, egfr, jak1, jak2 and lck demonstrating it as a selective inhibitor. it is also found to be an inhibitor of tubulin polymerization through binding to the unique confirmation on heterodimeric tubulin. in cellular assays, kx2-391 shows growth inhibition in nih3t3/c-src527f cells and syf/c-src527f cells with gi50 values of 23nm and 39nm, respectively [1, 2].since src acts as a regulator in cell proliferation survival, motility and invasiveness, kx2-391 is potent against a variety of solid tumors and many leukemia tumors. it is shown to inhibit primary tumor growth and to suppress metastasis [2].
References
[1] fallah-tafti a, foroumadi a, tiwari r, et al. thiazolyl n-benzyl-substituted acetamide derivatives: synthesis, src kinase inhibitory and anticancer activities. european journal of medicinal chemistry, 2011, 46(10): 4853-4858.
[2] naing a, cohen r, dy g k, et al. a phase i trial of kx2-391, a novel non-atp competitive substrate-pocket-directed src inhibitor, in patients with advanced malignancies. investigational new drugs, 2013, 31(4): 967-973.
