IACS-9571 hydrochloride is a potent, selective dual TRIM24-BRPF1 bromodomain inhibitor with Kd of 31 and 14 nM, respectively. IACS-9571 displays 9- and 21-fold selectivity against BRPF2 and BRPF3, weaker affinities with BAZ2B (Kd= 400 nM) and the second domain of TAF1 (Kd=1,800 nM), and >7,700-fold selectivity versus BRD4 BD1 and BD2. IACS-9571 demonstrates excellent cellular potency (EC50= 50 nM) and favorable pharmacokinetic properties. IACS-9571 is a chemical probe to investigate biological and pharmacological role of TRIM24 and/or BRPF1 bromodomain inhibition in vitro and in vivo.
