MK2 inhibitors

Target and Target Class: Mitogen-activated protein kinase-activated protein kinase 2 (MK2); Kinase

Indication: Inflammatory diseases

Rationale

MK2 is a validated kinase target in the p38α MAPK pathway, downstream of p38α and immediately upstream of Hsp27 and tristetraprolin (TTP). TTP is a key stability factor of cytokine mRNA and direct phosphorylation of TTP by MK2 leads to increased gene transcription and thus cytokine production. Inhibitors of MK2 have been shown to suppress the secretion of TNFα in appropriate in vivo models.. Therefore, MK2 inhibitors are postulated to be of use in treating diverse inflammatory conditions, including rheumatoid arthritis.

Status

Evotec has identified active MK2 inhibitors following a fragment-based screen and is currently optimizing these inhibitors.