METHOD OF MODULATING STRESS-ACTIVATED PROTEIN KINASE SYSTEM

摘要

It has now been discovered that a high therapeutic effect in treating various disorders associated with enhanced activity of kinase p38 may be achieved by using a potent p38alpha kinase inhibitor compound which also has inhibitory activity against p38gamma. Furthermore, reducing the activities of both kinase p38gamma and kinase p38alpha without reducing the activity of a kinase p38alpha to such an extent that undesired side effects are observed upon administration to a subject having a disorder associated with enhanced activity of kinase p38 has been discovered to be achievable by modifying inhibitors of p38alpha such that the modification engenders inhibitory activity against p38gamma. Described are compounds with activity against p38alpha and p38gamma. Disclosed are methods of using described compounds and compositions to modulate a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits inhibition of the p38gamma and p38alpha MAPKs. Also disclosed are methods for identifying compounds which inhibit p38gamma and p38alpha MAPKs and which can modulate a stress activated protein kinase (SAPK) system.