// Yukiyo Tada 1,2 , Shoichiro Kokabu 1 , Goro Sugiyama 1 , Chihiro Nakatomi 1 , Kazuhiro Aoki 3 , Hidefumi Fukushima 4 , Kenji Osawa 5 , Yasutaka Sugamori 3 , Keiichi Ohya 3 , Masato Okamoto 6 , Tomoyuki Fujikawa 7 , Akiko Itai 7 , Kou Matsuo 8 , Seiji Watanabe 2 and Eijiro Jimi 1,9 1 Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan 2 Division of Dental Anesthesiology, Department of Control of Physical Functions, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan 3 Section of Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan 4 Department of Physiological Sciences and Molecular Biology, Fukuoka Dental College, Fukuoka, Tamura, Sawara-ku, Fukuoka, Japan 5 Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka-shi, Saitama, Japan 6 Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Shirokane, Minato-ku, Tokyo, Japan 7 Institute of Medical Molecular Design Inc (IMMD Inc), Hongo, Bunkyo-ku, Tokyo, Japan 8 Division of Oral Pathology, Department of Health Promotion, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan 9 Center for Oral Biological Research, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan Correspondence: Eijiro Jimi, email: // Keywords : NF-κB, IMD-0560, bone invasion, oral squamous cell carcinoma Received : September 16, 2014 Accepted : October 28, 2014 Published : October 28, 2014 Abstract Oral squamous cell carcinoma (OSCC) cells display significantly augmented nuclear factor-κB (NF-κB) activity, and inhibiting this activity suppresses malignant tumor characteristics. Thus, we evaluated the effect of IMD-0560, a novel inhibitor of IκB kinase (IKK) β that is under assessment in a clinical trial of rheumatoid arthritis, on bone invasion by the mouse OSCC cell line SCCVII. We examined the inhibitory effects of IMD-0560 on NF-κB activity and tumor invasion using human OSCC cell lines and SCCVII cells in vitro . Using a mouse model of jaw bone invasion by SCCVII cells, we assessed the inhibitory effect of IMD-0560 on jaw bone invasion, tumor growth, and matrix degradation in vivo . IMD-0560 suppressed the nuclear translocation of NF-κB and the degradation of IκBα in OSCC cells. IMD-0560 also inhibited invasion by suppressing matrix metalloproteinase-9 (MMP-9) production in OSCC cells. IMD-0560 protected against zygoma and mandible destruction by SCCVII cells, reduced the number of osteoclasts by inhibiting receptor activator of NF-κB ligand (RANKL) expression in osteoblastic cells and SCCVII cells, increased SCCVII cell death and suppressed cell proliferation and MMP-9 production in SCCVII cells. Based on these results, IMD-0560 may represent a new therapeutic agent for bone invasion by OSCC cells.