Description
MS645 (MS-645) is a novel, bivalent bromodomain (BRD) inhibitor with Ki of 18.4nM for tandem BD1-BD2 (BRD4 BD1/BD2), shows12- to 28-fold gain in affinity for binding to the tandem BD1-BD2 over the single BD1 or BD2; shows comparable potency to the tandem BD1-BD2 of BRD2 and BRD3 as to that of BRD4; inhibits the transcription of BRD4 target gene IL-6 in MDA-MB-231 cells with 70% inhibition at 20nM, much higher than 20-30% inhibition by JQ1 and MS417; potently inhibits cell growth of a panel TNBC with IC50 of 4-20nM, blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors JQ1