Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.