a-ra-f

alpha-RA-F can modulate collagen synthesis and matrix metalloproteinases (MMPs) expression levels by boosting collagen synthesis and reducing MMPs expression levels in human fibroblasts without cytotoxicity.

RPR-200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb c mice (ED50 = 6 mg kg). At oral doses between 10 and 30 mg kg day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies.