MAP Kinase p38Inhibitors: Clinical Results and an Intimate Look at Their Interactions with p38alpha Protein
Current Medicinal Chemistry, (December 2005)DOI: doi:10.2174/092986705774462914
Abstract
Mitogen-activated protein kinase p38 is a serine/threonine kinase originally isolated from lipopolysaccharide (LPS) stimulated monocytes. There are four isoforms p38agr inhibitors as potential treatment for inflammatory diseases. Herein we provide a brief overview of recent reported clinical results for AMG 548, BIRB 796, VX 702, SCIO 469, and SCIO 323. However, our focus will be on the binding modes of these inhibitors and other p38 inhibitors in the recent literature.
Description
p38 MAPK ~ Current Research (2005)
Amgen:
Phase I, AMG 548. Arthritis. Trial with healthy males revealed elevated liver enzymes in 9 out of 54 subjects; random, isolated, not dose or exposure dependent. Further development suspended.
Boehringer Ingelheim:
Phase II, BIRB 796. Rheumatoid arthritis, Crohn's disease, psoriasis. Elevated liver enzymes (9 out of 48). Further development suspended.
Scios (Johnson & Johnson):
Phase II, SCIO 469. Pain, multiple myeloma, rheumatoid arthritis. Significant anti-nociceptive effects in acute pain.
Phase I, SCIO 323. Myelodysplastic syndrome, multiple myeloma, rheumatoid arthritis, cerebral ischemia, diabetes mellitus.
Vertex.
VX-702. Rheumatoid arthritis, Crohn's disease, inflammatory cardiovascular disorders. Signiificantly lowers C-reactive protein in acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), remaining significantly lower 4 weeks beyond last dose.