CF53 is a highly potent, selective, and orally active inhibitor of BET protein, with a Ki of <1 nM, Kd of 2.2 nM, and an IC50 of 2 nM for BRD4 BD1. CF53 binds to both the BD1 and BD2 domains of BRD2, BRD3, BRD4, and BRDT BET proteins with high affinities, being very selective over non-BET bromodomain-containing proteins. CF53 exhibits potent anti-tumor activity both in vitro and in vivo.

BRD4 BD2:0.8 nM (kd), BRD3 BD1:0.52 nM (kd), BRD2 BD1:1.1 nM (kd), BRD3 BD2:0.49 nM (kd), CREBBP:47 nM (kd), BRDT BD2:1 nM (kd), CECR2:570 nM (kd), BRD2 BD2:0.6 nM (kd), BRD4 BD1:2.2 nM (kd), BRDT BD1:2 nM (kd), BRD4 BD1:2 nM, EP300:110 nM (kd)

CF53 exhibits high binding affinities to the BD1 and BD2 domains of BRD2, BRD3, BRD4, and BRDT within the BET protein family, with dissociation constants (Kds) as follows: 1.1 nM for BRD2 BD1, 0.6 nM for BRD2 BD2, 0.52 nM for BRD3 BD1, 0.49 nM for BRD3 BD2, 0.8 nM for BRD4 BD2, 2 nM for BRDT BD1, and 2.1 nM for BRDT BD2. Additionally, it displays Kds of 47 nM, 570 nM, and 110 nM for CREBBP, CECR2, and EP300, respectively. In terms of biological activity, CF53 shows IC50 values of 7 nM and 85 nM against MOLM-13 acute leukemia and MDA-MB-231 breast cancer cell lines, respectively[1].

CF53, administered orally at doses of 25 and 50 mg/kg, demonstrates strong anti-tumor efficacy in both the MDA-MB-231 xenograft tumor model and the RS4;11 model in mice[1].