INCB-057643

INCB-057643 is a novel, orally bioavailable BET inhibitor. IC50 & Target: BET^[1] In Vitro: INCB-057643 is a novel, orally bioavailable BET inhibitor. INCB-057643 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 INCB-057643 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 INCB-057643^[1]. In Vivo: Production of several cytokines, including IL-6, IL-10 and MIP-1α, is repressed by INCB-057643 in human and mouse whole blood stimulated ex vivo with LPS. Oral administration of INCB-057643 results in significant anti-tumor efficacy in xenograft models of AML, myeloma, and DLBCL. Additionally, combining INCB-057643 with standard of care agents used for the treatment of DLBCL including rituximab and bendamustine results in enhanced anti-tumor efficacy relative to that achieved with single agent therapies at doses that are well tolerated^[1].