Triple-negative　breast　cancer　(TNBC)　is　one　of　the　most　malignant　breast　cancers　currently　with　a　lack　of　targeted　therapeutic　drugs.　Accumulating　evidence　supports　that　KLF5　represents　a　novel　therapeutic　target　for　the　treatment　of　basal　TNBC.　Our　previous　studies　revealed　that　mifepristone　is　capable　of　suppressing　TNBC　cell　proliferation　and　promoting　cancer　cell　apoptosis　by　inhibiting　KLF5　expression.　Nevertheless,　its　anticancer　efficacy　is　only　modest　with　high　dose.　Moreover,　its　main　metabolite　N-desmethyl　mifepristone　with　the　removal　of　one　methyl　moiety　results　in　a　significant　loss　of　anti　proliferative　activity,　indicating　an　important　pharmacophore　domain　around　this　methyl　moiety.　To　improve　the　pharmacokinetic　properties　including　metabolic　stability　and　enhance　the　anticancer　activities,　a　focused　compound　library　by　altering　this　sensitive　metabolic　region　of　mifepristone　has　been　designed　and　synthesized　for　scaffold　repurposing　and　structural　optimization.　Compound　17　(FZU-00,004)　has　been　identified　with　an　attractive　anticancer　profile　against　TNBC　via　suppressing　KLF5　expression.　(C)　2018　Elsevier　Masson　SAS.　All　rights　reserved.