Pamapimod

449811-01-2

406.38

DMSO : >= 34 mg/mL (83.67 mM)

MAPK/ERK Pathway; Autophagy

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 p38alpha and p38beta, respectively. Pamapimod has no activity against p38delta or p38gamma 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-alpha is inhibited by Pamapimod, with an EC₅₀ of 25 nM. Pamapimod suppresses TNF-alpha and IL-1beta production in whole blood, with EC₅₀ values of 0.40 and 0.10 uM, 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].