PLX51107 is a potent and selective BET inhibitor (Kds: 1.6, 2.1, 1.7, and 5 nM for BRD2-BD1, BRD3-BD1, BRD4-BD1, and BRDT-BD1).

BRDT BD2:120 nM (Kd), BRD4 BD2:6.1 nM (Kd), BRD3 BD1:2.1 nM (Kd), BRDT BD1:5 nM (Kd), BRD4 BD1:1.7 nM (Kd), BRD3 BD2:6.2 nM (Kd), BRD2 BD2:5.9 nM (Kd), BRD2 BD1:1.6 nM (Kd)

PLX51107是一种BET抑制剂，对BRD2、BRD3、BRD4和BRDT的BD1的Kds分别为1.6、2.1、1.7和5 nM，对BD2的Kds分别为5.9、6.2、6.1和120 nM。PLX51107还与CBP和EP300的溴结构域相互作用(Kd约在100 nM范围内)。PLX51107（0.156-10 μM）抑制初级慢性淋巴细胞性白血病（CLL）细胞的CpG诱导增殖。此外，PLX51107还导致p21和IκBα的积累，降低c-MYC水平，并调控促凋亡和抗凋亡蛋白。

PLX51107（2 mg/kg，p.o.）在Ba/F3（小鼠IL3依赖的前B细胞系）脾肿大模型中通过口服抑制脾肿大75%，效果与25 mg/kg OTX015相似。PLX51107（20 mg/kg，每日一次，p.o.）通过每日一次口服，在侵袭性CLL和Richter转化（RT）疾病模型中展现出强大的抗白血病效果。

For engraftment studies, C57BL/6 WT mice are engrafted with 1E7 cells by tail-vein injection of splenocytes derived from Eμ-TCL1 or Eμ-Myc/TCL1 mice with active disease. At the onset of leukemia (Eμ-TCL1: ≥ 10% CD19/CD5/CD45-positive circulating cells; Eμ-Myc/TCL1: WBC count ≥ 8 and/or ≥ 5% CD19/CD5/CD45-positive circulating cells), mice are randomized to receive treatments as indicated. PLX51107 20 mg/kg, qd (once daily), oral gavage. Vehicle = 10% N-methyl-2-pyrrolidone plus diluent (40% PEG400, 5% TPGS, 5% Poloxamer 407, and 50% water). Mice are sacrificed when meeting early removal criteria (>20% weight loss, impaired motility, splenomegaly, and evident tumor masses), and tissues are collected for further analysis.