Description
InformationPLX51107 PLX51107 is as a novel BET inhibitor with modest preference for bromodomain-1 (BD1) versus bromodomain-2 (BD2) within each BET protein (Kd = 1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1 and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively. Among non-BET proteins, PLX51107 shows significant interactions only with the bromodomains of CBP and EP300 (p300) (Kd in the 100 nM range).TargetsBRD2 BD1 (Cell-free assay); BRD4 BD1 (Cell-free assay); BRD3 BD1 (Cell-free assay); BRDT BD1 (Cell-free assay); BRD2 BD2 (Cell-free assay) 31640,1.6 nM(Kd); 1.7 nM(Kd); 2.1 nM(Kd) ;5 nM(Kd); 5.9 nM(Kd)In vitroIn a set of cell cultures, short-term (4h) treatment of PLX51107 result in robust change in PD markers but do not induce an immediate apoptotic response. Induction of apoptosis occurrs after prolonged treatment (16 hours or more of continuous exposure). PLX51107 induces accumulation of p21 and IκBα, reduced levels of cMYC, and modulation of pro- and anti-apoptotic proteins.In vivoPLX51107 is well tolerated in mice. The half-life of PLX51107 is relative short in rodents and dogs (<3 h). PLX51107 demonstrates in vivo antitumor effects in preclinical models of CLL and aggressive lymphoma