Selectivity of SB203580, SB202190 and Other Commonly Used p38 Inhibitors: Profiling Against a Multi-Enzyme Panel

The p38 mitogen-activated protein kinase (MAPK) plays an essential role in the normal inflammatory response, however chronic activation of p38 can lead to the development of inflammatory diseases. Several small molecule p38 inhibitors have been developed for the treatment of inflammatory diseases. These inhibitors are used extensively for understanding the requirements for p38 activity in many cellular processes. However, the selectivity of these inhibitors against enzymes outside of the MAPK family has not been broadly addressed. To investigate inhibitor selectivity we have screened several widely used, commercially available p38 inhibitors against a multi-enzyme panel and generated their selectivity profiles. We show that these inhibitors can have potent effects on multiple cellular signaling pathways and we discuss the implications of these findings.