NI-42 (compound 13-d), a structurally orthogonal chemical probe for the BRPFs, is a biased, potent inhibitor of the BRD of the BRPFs (IC50s of BRPF1/2/3=7.9/48/260 nM; Kds of BRPF1/2/3=40/210/940 nM) with excellent selectivity over nonclass IV BRD proteins[1]. BRPF1|7.9 nM (IC50)|BRPF2|48 nM (IC50)|BRPF3|260 nM (IC50)|BRPF1|40 nM (Kd)|BRPF2|210 nM (Kd)|BRPF3|940 nM (Kd)|BRD4 (BD1)|4500 nM (IC50)|BRD7|82 nM (IC50)|BRD9|310 nM (IC50)|BRD9|1130 nM (Kd)
NI-42 shows IC50s of 82, 310, and 4500 nM for BRD7, BRD9, and BRD4 (BD1), respectively, and has a Kd of 1130 nM for BRD9[1].
[1]. Igoe N, et al. Design of a Biased Potent Small Molecule Inhibitor of the Bromodomain and PHD Finger-Containing (BRPF) Proteins Suitable for Cellular and in Vivo Studies. J Med Chem. 2017 Jan 26;60(2):668-680.