Staurosporine, a potent inhibitor of $\text{phospholipid}\text{Ca}{}^{\mathrm{++}}\text{dependent}$ protein kinase

Abstract

Staurosporine, microbial alkaloid which has been known to have anti-fungal activity was found to inhibit markedly $\text{phospholipid}\text{Ca}{}^{\mathrm{++}}\text{dependent}$ protein kinase (protein kinase C) from rat brain, with an IC₅₀ value of 2.7 nM. However, it had little effect on the binding of ³H-phorbol-12, 13-dibutyrate (PDBu) to protein kinase C. The inhibition of protein kinase C was not competitive with phospholipid. This compound also showed the strong cytotoxic effect on the growth of HeLa S3 cells, with an IC₅₀ value of 4 × 10⁻¹²M under the condition of 72 hr-exposure.