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

The study aims to determine if BAZ2-ICR (Compound 13) is capable of displacing BAZ2 bromodomains from chromatin within live cells. A fluorescence recovery after photobleaching (FRAP) assay, employing a GFP-tagged full-length BAZ2A protein transfected into human osteosarcoma (U2OS) cells, was conducted. The results show that 1 μM BAZ2-ICR significantly shortens the recovery time of the wild-type (wt) construct to a level comparable to that of the dominant negative mutant. This indicates that BAZ2-ICR effectively inhibits BAZ2A's function in cells[1].

BAZ2-ICR, administered at a dose of 5 mg/kg, demonstrates a 70% bioavailability with moderate clearance—approximately 50% of mouse liver blood flow—and an adequate volume of distribution[1]. As Compound 13, it exhibits exceptional solubility (25 mM in D2O) and a log D value of 1.05, indicating favorable distribution between lipophilic and aqueous phases. Furthermore, it shows high stability in mouse microsomes and effective permeation in the CaCo-2 model, presenting a profile appropriate for both oral and intravenous administration.