AOPs Including This Stressor
|Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)||Moderate|
Events Including This Stressor
|Inhibition of Fyna|
|User term||DTXID||Preferred name||Casrn||jchem_inchi_key||indigo_inchi_key|
There is no evidence text for this AOP
Staurosporine is a microbial alkaloid isolated from Streptomyces sp. (Omura, S.,1977) which has been shown to be a potent broad-range inhibitor competing with ATP, but not peptide substrate, for binding to protein kinases including Fyn kinase. Staurosporine binds to the ATP-binding site of Fyn (Kinoshita et al., 2006) and has nanomolar potency against most protein kinases including Fyn. This level of selectivity has already enabled staurosporine to be used as a lead inhibitor for the design of specific potent protein kinase inhibitors (Toullec et al., 1991).
Characterization of Exposure
Omura, S., Iwai, Y., Hirano, A., Nakagawa, A., Awaya, J., Tsuchya, H., Takahashi, Y. & Masuma, R. (1977). New alkaloid AM-2282 of Streptomyces origin - tax- onomy, fermentation, isolation and preliminary characterisation.
Kinoshita, T., Matsubara, M., Ishiguro, H., Okita, K., & Tada, T. (2006). Structure of human Fyn kinase domain complexed with staurosporine. Biochemical and Biophysical Research Communications, 346(3), 840–844. https://doi.org/10.1016/j.bbrc.2006.05.212
Toullec, D., Pianetti, P., Coste, H., Bellevergue, P., Grand-Perret, T., Ajakane, M., Baudet, V., Boissin, P., Boursier, E., Loriolle, F., Duhamel, L., Charon, D., & Kirilovsky, J. (1991). The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. Journal of Biological Chemistry, 266(24), 15771–15781. https://doi.org/10.1016/s0021-9258(18)98476-0