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.
Mulqueen
M J
MJ
Department of Anti-inflammatory Biology, Roche Products Ltd., Welwyn Garden City, Herts., England.
Bradshaw
D
D
Davis
P D
PD
Elliott
L
L
Griffiths
T A
TA
Hill
C H
CH
Kumar
H
H
Lawton
G
G
Nixon
J S
JS
Sedgwick
A D
AD
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D017252:CD3 Complex / Q000187:drug effects; D002417:Cattle; D015536:Down-Regulation; D004487:Edema / Q000188:drug therapy; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D010764:Phosphorylase Kinase / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017252:CD3 Complex; D007211:Indoles; D008301:Maleimides; C076005:Ro 31-8830; D010764:Phosphorylase Kinase; D011493:Protein Kinase C