PLX51107

PLX51107 is a potent and selective small molecule inhibitor of the bromodomain and extraterminal (BET) protein family, with particular selectivity for bromodomain-containing protein 4 (BRD4). It binds to the acetylated lysine recognition motifs in the bromodomains of BRD4 and other BET proteins (including BRD2, BRD3, and BRDT), preventing their interaction with acetylated histones. This disrupts chromatin remodeling and gene expression by inhibiting transcriptional regulators involved in cellular proliferation. The inhibition of these pathways can induce apoptosis and inhibit proliferation in tumor cells overexpressing BET proteins. Preclinical studies have shown antileukemic effects in models of chronic lymphocytic leukemia (CLL), Richter transformation (RT), as well as activity against acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), graft-versus-host disease (GVHD), and solid tumors[1][2][3][6][7]. Developed originally by Plexxikon/Daiichi Sankyo, clinical development has included trials for hematological malignancies such as AML/MDS and steroid-refractory acute GVHD; however, recent updates indicate discontinuation or termination of these programs[7].

Other names

BRD4 inhibitor PLX51107BRD-4 inhibitor PLX51107BRD 4 inhibitor PLX51107(S)-4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid