Known because of the structural Similarity between the class of compounds with p3 8-MAP kinase inhibitor SB203580, CGH2466 was also tested for the inhibition of p38 MAP kinase and other kinases. CGH2466 showed inhibition of P38B p38a and tested but no inhibition of other kinases. Two of the four isoforms of p38 MAP kinase is known to Flt Signaling be important in the processes. Essential to the inflammatory response and tissue remodeling P38 MAP kinases important in monocytes and macrophages and P38A and P38B are best known for their effects on the production of TNF and signaling. Moreover, the production and action of mediators of most potential airway inflammation were found to be dependent Ngig p38 MAP kinase cascade. Moreover p38 MAP kinase inhibitors have also been shown to reduce persistent airway eosinophilia and apoptosis of eosinophils, activity th, Which added a mechanism can provide through the p38 MAP kinase inhibitors have therapeutic utility in chronic inflammation provide airways .
CGH2466 may be a potent inhibitor of TNF and IFN-g production, however, is most likely due to a combination of the inhibition of p38 MAP kinase and inhibition of PDE4. Moreover, this compound was also more active than p38 MAP kinase inhibitor SB203580 both in vivo models of the airway eosinophil and neutrophil infiltration. ABT-492 Concluding End, in the search for improved theophylline with gr Erer efficiency, we have a compound that combines the antagonism of adenosine receptors, p38 MAP kinase and the inhibition of PDE4 discovered and demonstrated potent anti-inflammatory effects in vitro and in vivo.
This combination of activity T seem to be much more effective than CGH2466 has a pronounced Gte inflammatory response compared to ACE inhibitors more selective or nonselective adenosine receptor antagonists, alone. Zus Tzlich because of its selectivity t for certain subtypes of adenosine receptors and PDE4 isoenzymes may CGH2466 have a better side effect profile than theophylline. Thus CGH2466, targeting key mechanisms bekannterma S is involved in chronic inflammatory airway responses may provide a therapeutic benefit in lung diseases such as asthma and COPD. The survival of smooth vascular Myocytes h Depends on the balance between proliferation and apoptosis, and aberrant regulation of these pathways in the proliferation of Vaskul Ren disorders such as pulmonary hypertension, a disease involved by progressive remodeling in distal pulmonary arteries.
The attention is focused on therapies that inhibit proliferation and resistance to apoptosis in smooth muscle cells of the pulmonary arteries. The omnipresent Rtige second messenger adenosine monophosphate is a potential target because it is one of the most important factors intracellular Ren embroidered slow cell proliferation and apoptosis. Prostacyclin analogs are acting for a vasodilator PDT Haupt Chlich over IP receptors to adenylate cyclase and intracellular Ren stimulate cAMP levels produced, but also anti-proliferative actions on human PASMCs k this May be important for their long-term effects in vivo.