BAZ2-ICR is an epigenetic chemical probe and it also is a potent, selective, cell active and orally active BAZ2A/B bromodomains inhibitor with IC50s of 130 nM and 180 nM, and Kds of 109 nM and 170 nM, respectively. BAZ2-ICR shows 10-15-fold selectivity for binding BAZ2A/B over CECR2 and >100-fold selectivity over all other bromodomains.

BAZ2A:（kd）109 nM, BAZ2A:130 nM, BAZ2A:170 nM（kd）, BAZ2B:180 nM

To investigate whether BAZ2-ICR (Compound 13) can displace BAZ2 bromodomains from chromatin in living cells. A fluorescence recovery after photobleaching (FRAP) assay utilizing GFP-tagged BAZ2A full length protein transfected into human osteosarcoma cells (U2OS) are tested. 1 μM BAZ2-ICR reduces the recovery time of the wild-type (wt) construct to a level similar to the dominant negative mutant, confirming that BAZ2-ICR inhibits BAZ2A in cells[1].

BAZ2-ICR (5 mg/kg) shows 70% bioavailability and moderate clearance (～50% of mouse liver blood flow) and volume of distribution[1]. BAZ2-ICR (Compound 13) shows very high solubility (25 mM in D2O), a measured log D of 1.05. High stability in mouse microsomes, and permeation in the CaCo-2 model and thus a suitable profile for oral and intravenous gavage.