Mivebresib

Mivebresib (ABBV-075) is a potent and orally available BET bromodomain inhibitor with Ki of 1.0, 12.2, 1.5, and 2.2 nM for BRD2, BRD3, BRD4 and BRDT, respectively; displays 54-fold selectivity over EP300, has potential weak activity against SMARCA4 (70% inhibition at 1 uM), Kd >1 uM for 18 other bromodomains; exhibits inhibition of c-Myc expression and displacing BRD4 from the Myc promoter; dose-dependently inhibits IL-6 concentration in a murine model of LPS-induced endotoxic shock, shows vivo antitumor efficacy in a Kasumi-1 AML mouse xenograft model.Breast Cancer Phase 1 Clinical (In Vitro) :Mivebresib inhibit DHT-stimulated transcription of AR target genes without significant effect on AR protein expression. In addition to blocking the transcription activation downstream of AR, Mivebresib is also a potent inhibitor of MYC and the TMPRSS2-ETS fusion proteins.