CC-99677

CC-99677 is an oral, highly selective small molecule inhibitor of MAPK-activated protein kinase 2 (MK2), originally developed by Celgene and subsequently by Bristol Myers Squibb. MK2 is a key downstream effector of the p38 mitogen-activated protein kinase (MAPK) pathway, which plays a central role in the regulation of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-17. By targeting MK2 rather than p38 directly, CC-99677 aims to achieve sustainable multi-cytokine inhibition while potentially avoiding the off-target toxicities and tachyphylaxis associated with direct p38 inhibitors. The drug was primarily investigated for the treatment of chronic inflammatory conditions, including ankylosing spondylitis, psoriasis, and psoriatic arthritis. However, development was discontinued by Bristol Myers Squibb in early 2023 following Phase 2 clinical evaluations.