Background:

AL8697 is a selective p38 MAPK(mitogen-activated protein Kinase) inhibitor, which is also named P38 α inhibitor. It has the function of inhibiting the activity of P38 MAPK.[1]

Mitogen activated protein kinases (MAPK) are a group of signaling molecules that appear to play important roles in inflammatory processes. The P38 MAPK is one of the best described MAPK cascades. The p38 MAPK plays a key role in both the synthesis and the signalling of pro-inflammatory cytokines such as TNFa and IL-6 by monocyte/macrophages. The p38 MAPK are involved in the up-regulation of TNF production by murine macrophages.It has high activity in cardiovascular cells under a variety of cellular stresses. In cardiovascular disease, the P38 MAPK signaling pathways are activated.[2,3]

AL8697 function by the inhibition of P38 MAPK. It regulates a variety of cell activities related with P38 MAPK.

In a rat adjuvant-induced arthritis model, AL8697 exhibited a good anti-inflammatory effect and induced leukocytosis and increased total plasma cholesterol, these properties were evidently at 10 mg/kg. In addition, AL8697 partially restored the platelet count. The complex profile for AL8697 in rat AIA (adjuvant-induced arthritis) is not observed in human RA (rheumatoid arthritis).[1]

参考文献:
[1].  Balagué C, Pont M, Prats N, Godessart N. Profiling of dihydroorotate dehydrogenase, p38 and JAK inhibitors in the rat adjuvant-induced arthritis model: a translational study. Br J Pharmacol. 2012 Jun;166(4):1320-32
[2].  Ajizian SJ, English BK, Meals EA.Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J Infect Dis. 1999 Apr;179(4):939-44.
[3].   Bao W, Behm DJ, Nerurkar SS, Ao Z, et al. Effects of p38 MAPK Inhibitor on angiotensin II-dependent hypertension, organ damage, and superoxide anion production. J Cardiovasc Pharmacol. 2007 Jun;49(6):362-8.