1. Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.
- Author
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Mulqueen MJ, Bradshaw D, Davis PD, Elliott L, Griffiths TA, Hill CH, Kumar H, Lawton G, Nixon JS, and Sedgwick AD
- Subjects
- Administration, Oral, Animals, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Blood Platelets drug effects, Blood Platelets enzymology, CD3 Complex drug effects, Cattle, Down-Regulation, Edema drug therapy, Female, Humans, In Vitro Techniques, Indoles administration & dosage, Male, Maleimides administration & dosage, Mice, Phosphorylase Kinase antagonists & inhibitors, Rabbits, Rats, T-Lymphocytes drug effects, T-Lymphocytes immunology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Indoles pharmacology, Maleimides pharmacology, Protein Kinase C antagonists & inhibitors
- Abstract
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.
- Published
- 1992
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