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The excessive osteoclast activity in the metastatic bone lesions often produces osteolysis. The cyclic\u2010AMP (cAMP)\u2010response element binding protein (CREB) serves a variety of biological functions including the transformation and immortalization of breast cancer cells. In addition, evidence has shown that CREB plays a key role in osteoclastgenesis and bone resorption. Small organic molecules with good pharmacokinetic properties and specificity, targeting CREB\u2010CBP (CREB\u2010binding protein) interaction to inhibit CREB\u2010mediated gene transcription have attracted more considerations as cancer therapeutics. We recently identified naphthol AS\u2010E (nAS\u2010E) as a cell\u2010permeable inhibitor of CREB\u2010mediated gene transcription through inhibiting CREB\u2010CBP interaction. In this study, we tested the effect of nAS\u2010E on breast cancer cell proliferation, survival, migration as well as osteoclast formation and bone resorption in vitro for the first time. Our results demonstrated that nAS\u2010E inhibited breast cancer cell proliferation, migration, survival and suppressed osteoclast differentiation as well as bone resorption through inhibiting CREB\u2010CBP interaction. In addition, the in vivo effect of nAS\u2010E in protecting against breast cancer\u2010induced osteolysis was evaluated. Our results indicated that nAS\u2010E could reverse bone loss induced by MDA\u2010MB\u2010231 tumour. These results suggest that small molecules targeting CREB\u2010CBP interaction to inhibit CREB\u2010mediated gene transcription might be a potential approach for the treatment of breast cancer bone metastasis.<\/jats:p>","DOI":"10.1111\/jcmm.14024","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T08:39:13Z","timestamp":1542789553000},"page":"1224-1234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Small molecule nAS\u2010E targeting cAMP response element binding protein (CREB) and CREB\u2010binding protein interaction inhibits breast cancer bone metastasis"],"prefix":"10.1111","volume":"23","author":[{"given":"Min","family":"Jiang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory for Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai 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