THE DEVELOPMENT OF MK2 INHIBITOR: WHERE DOES IT STAND?

Abstract

Drug development targeting protein kinases is the second most important group of drug target after G-protein coupled receptor which codes 22% of the druggable human genome. The protein kinases are key players in signal transduction, which regulate many different cellular processes in a tightly controlled manner through reversible phosphorylation. Several drugs that inhibit protein kinases have been in clinical use for the treatment of cancer. Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP KINASE 2) is one such kinase activated by p38MAPK , which plays a pivotal role in the regulation of inflammation and associated diseases diversifying it from other p38MAPK regulated signaling pathway. Considering the toxicity and side effects of p38MAPK inhibition, in the last decade, efforts were undertaken to develop different classes of MK2 inhibitor for therapeutic interventions as an alternative to the direct inhibition of p38MAPK . This review article describes the biology and mechanism of action of MK2, its role in inflammation and the development of small molecular inhibitor of MK2 highlighting opportunities and challenges in drug development targeting such type of kinases. The development of small molecule MK2 inhibitor will provide a better and safe therapeutic option in future.