Biological Activity
kx1-004 is a non-atp competitive inhibitor of pp60c-src with ic50 value of 40 μm [1].kx1-004 is a close analog of the indole-based src-ptk inhibitors reported previously. it has a 5-fluoro group and showed potent inhibition activity in isolated src-ptk assay. kx1-004 was found to have protective effect in noise-induced hearing loss. the chinchillas treated with 30 μm kx1-004 were exposed to continuous noise. and the results showed that treated ears exhibited up to 40 db less threshold shift (tts) and up to 25 db less permanent threshold shift (pts) than control ears. kx1-004 treatment also significantly reduced outer hair cell (ohc) loss than control. besides that, kx1-004 was proved to reduce the hearing loss and hair cell loss associated with impulse noise exposure markedly [1, 2].
References
[1] harris k c, hu b, hangauer d, et al. prevention of noise-induced hearing loss with src-ptk inhibitors. hearing research, 2005, 208(1): 14-25.
[2] milkiewicz k l, marsilje t h, woodworth jr r p, et al. the design, synthesis and activity of non-atp competitive inhibitors of pp60 c-src tyrosine kinase. part 2: hydroxyindole derivatives. bioorganic & medicinal chemistry letters, 2000, 10(5): 483-486.
