Malignant　melanoma,　the　most　deadly　form　of　skin　cancer,　has　a　high　propensity　for　metastatic　spread　and　is　notoriously　chemotherapy-resistant.　Metapristone　is　the　primary　metabolite　of　mifepristone　(RU486)　and　shows　biological　activities　similar　to　RU486.　In　the　present　study,　we　comprehensively　investigated　the　efficacy　of　metapristone　as　a　metastatic　chemopreventive　against　melanoma　B16F10　cells　in　vitro　and　in　vivo,　and　evaluated　the　safety　profile　of　both　drugs　in　mice.　Metapristone　showed　less　cytostatic　effect　in　vitro　and　in　vivo　in　comparison　with　mifepristone.　However,　metapristone　interfered　the　adhesion　of　B16F10　cells　to　fibronectin　by　down-regulating　cellular　expression　of　integrin　alpha　4.　Chemopreventive　pretreatment　followed　by　oral　administration　of　metapristone　and　mifepristone　(2.5,　10,　50　mg/kg/day　for　35　days)　to　melanoma　C57BL/6　mouse　model　showed　significant　attenuation　of　pulmonary　metastatic　development.　Oral　administration　of　high　doses　of　metapristone　and　mifepristone　to　normal　mice　for　35　days　(25,　100,　250　mg/kg/day)　resulted　in　a　dose-dependent　increase　in　mouse　liver　weight　that　was　more　severe　with　mifepristone　than　metapristone.　The　long-term　toxicity　study　revealed　more　changes　by　mifepristone　in　counts　of　erythrocytes,　leukocytes　and　platelets　than　by　metapristone.　In　conclusion,　metapristone　may　fit　into　a　new　class　of　cancer　metastatic　chemopreventive　agents.　It　showed　a　safety　and　efficacy　profile　better　than　mifepristone.　(C)　2016　Elsevier　Masson　SAS.　All　rights　reserved.