Pamapimod

Pamapimod (Ro4402257) is a potent, selective and orally active p38 MAPK inhibitor with IC₅₀s of 14 nM and 480 nM and K_is of 1.3 nM and 120 nM for p38α and p38β, respectively. Pamapimod has no activity against p38δ or p38γ isoforms. Pamapimod has the potential for rheumatoid arthritis and other autoimmune diseases treatment^[1]. In Vitro: Pamapimod binds to JNK kinases with K_i values of 190 nM, 16 nM and 19 nM for Jnk1, Jnk2 and Jnk3, respectively^[1].
After lipopolysaccharide (LPS) stimulation of the human myelomonocytic cell line (THP-1), secretion of TNF-α is inhibited by Pamapimod, with an EC₅₀ of 25 nM. Pamapimod suppresses TNF-α and IL-1β production in whole blood, with EC₅₀ values of 0.40 and 0.10 μM, respectively^[1]. In Vivo: Pamapimod (0-150 mg/kg; oral gavage; once daily; DBA/1J female mice) treatment reduces inflammation and bone loss in murine collagen-induced arthritis^[1].