[CAS NO. 1820889-23-3]  INCB057643

INCB057643 inhibits binding of BRD2/BRD3/BRD4 to an acetylated histone H4 peptide in the low nM range, and is selective against other bromodomain containing proteins. In vitro analyses show that INCB057643 inhibits proliferation of human AML, DLBCL, and multiple myeloma cell lines, with a corresponding decrease in MYC protein levels. Cell cycle analyses indicate that G1 arrest and a concentration-dependent increase in apoptosis are seen within 48 hours of treatment with INCB057643. Production of several cytokines, including IL-6, IL-10 and MIP-1α, was repressed by INCB057643 in human and mouse whole blood stimulated ex vivo with LPS. INCB057643 inhibits proliferation of prostate cancer cell lines. In short-term cell proliferation assays, INCB057643 appears more effective against androgen-dependent (VCaP and LNCaP) than androgen-independent (DU145 and PC3) cells.