Talmapimod (SCIO-469) is an orally active, selective, and ATP-competitive p38α inhibitor with IC₅₀ of 9 nM, shows about 10-fold selectivity over p38β, and at least 2000-fold selectivity over a panel of 20 other kinases, including other MAPKs. IC50 & Target: IC50: 9 nM (p38)^[1]. In Vitro: Talmapimod (SCIO-469) decreases constitutive p38α MAPK phosphorylation of both 5T2MM and 5T33MM cells. Talmapimod (SCIO-469) also inhibits secretion and expression of the osteoclast-activating factors IL-11, receptor activator of NF-κB ligand, and macrophage inflammatory protein 1α, and prevents human osteoclast activationIn. It can also inhibit multiple myeloma growth and prevents bone disease in the 5T2MM and 5T33MM models^[2].
Talmapimod (SCIO-469) inhibits LPS-induced TNF-a production in human whole blood^[3]. In Vivo: Targeting p38α MAPK with Talmapimod (SCIO-469) decreases myeloma burden in addition to preventing the development of myeloma bone disease^[2].