Staurosporine- Interesting Facts

Tuesday, June 13, 2017

Staurosporine (AM-2282) is a natural antibiotic, first isolated in 1977 from Streptomyces staurosporeus (Omura et al, 1977). Staurosporine displays strong inhibitory effect against a variety of kinases. In addition, Staurosporine and its analogues exhibit antifungul, antibacterial and immunosuppressive activities.

Staurosporine inhibit protein kinase C (PKC) by completely binding at the PKC ATP-binding site. Due to its strong inhibitory effect, Staurosporine is widely used as a PKC inhibitor in the research laboratory. However, its non-selectivity influence on different protein kinases causes a high level of cross-reactivity and prevents using Staurosporine as a drug (Park et al, 2013; Son et al, 2011).

During the last decades, some analogues of Staurosporine were isolated or synthesized in order to improve the its selectivity. An important analogue is K252a, isolated from culture of Nocardiopsis sp. Other semisynthetic analogues are K252b, K252c, KT5823, KT5555, KT5720 and PKC 412. The different analogues share a common structural component, display inhibitory effect on protein kinases, but differ at their inhibition's strength and enzyme's affinity.

 

 

 

References: 
  1.  Staurosporine analogues from microbial and synthetic sources and their biological activities., Park BS, Abdel-Azeem AZ, Al-Sanea MM, Yoo KH, Tae JS, Lee SH. Curr Med Chem. 2013;20(31):3872-902. PMID: 23848535 .
  2. Direct effect of protein kinase C inhibitors on cardiovascular ion channels., Son YK, Hong DH, Kim DJ, Firth AL, Park WS. BMB Rep. 2011 Sep;44(9):559-65. PMID: 21944247
  3. A new alkaloid AM-2282 of Streptomyces origin taxonomy, fermentation, isolation and preliminary characterization, Omura S, Iwai Y, Hirano A, Nakagawa A, Awaya J, Tsuchiya H, Takahashi Y, Masuma R. . J. Antibiot. 1977;  30 (4): 275–282. doi:10.7164/antibiotics.30.275. PMID 863788.