MLN120B dihydrochloride

MLN120B is an inhibitor of IκB kinase β (IKKβ; IC₅₀ = 45 nM).¹ It is selective for IKKβ over a panel of 30 tyrosine and serine/threonine kinases (IC₅₀s = >50 ?M for all). MLN120B inhibits NF-κB activation induced by phorbol 12-myristate 13-acetate with an IC₅₀ value of 2.8 ?M in a reporter assay. It inhibits proliferation in a panel of six multiple myeloma cancer cell lines, including cell lines resistant to dexamethasone , melphalan , or doxorubicin , in a concentration-dependent manner.² MLN120B (50 mg/kg) reduces serum levels of soluble human IL-6 receptor, a marker of INA-6 cell growth, in a SCID-hu mouse model of bone marrow-engrafted INA-6 multiple myeloma. It reduces paw swelling, as well as cartilage destruction and bone erosion in the inflamed joints, in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant (CFA) with a median effective dose (MED) of 12 mg/kg.³

1.Wen, D., Nong, Y., Morgan, J.G., et al.A selective small molecule IκB kinase β inhibitor blocks nuclear factor κB-mediated inflammatory responses in human fibroblast-like synoviocytes, chondrocytes, and mast cellsJ. Pharmacol. Exp. Ther.317(3)989-1001(2006) 2.Hideshima, T., Neri, P., Tassone, P., et al.MLN120B, a novel IκB kinase β inhibitor, blocks multiple myeloma cell growth in vitro and in vivoClin Cancer Res.12(19)5887-5894(2006) 3.Schopf, L., Savinainen, A., Anderson, K., et al.Iκκβ inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritisArthirits Rheum.54(10)3163-3173(2006)