BRPF1 Inhibitor

BAY-299, a chemical probe, is a very potent, dual inhibitor with IC₅₀s of 67 nM for BRPF2 bromodomains (BD), 8 nM for TAF1 BD2, and 106 nM for TAF1L BD2.

LT052 is a highly selective BET BD1 inhibitor with an IC₅₀ of 87.7 nM. LT052 exhibits nanomolar BRD4 BD1 potency and 138-fold selectivity over BRD4 BD2 (IC₅₀=12.130 μM). LT052 has anti-inflammatory?activity and can be used for acute gout arthritis research.

GSK9311, a less active analogue of GSK6853, can be used as a negative control. GSK9311 inhibits BRPF bromodomain with pIC₅₀ values of 6.0 and 4.3 for BRPF1 and BRPF2, respectively.

TRIM24/BRPF1-IN-2 (compound 20l) is a potent TRIM24/BRPF1 dual inhibitor, with IC₅₀ values of 0.98 and 1.16 μM, respectively. TRIM24/BRPF1-IN-2 shows TRIM24/BRPF1 bromodomain binding affinity. TRIM24/BRPF1-IN-2 can be used for prostate cancer research.

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; K_ds of BRPF1/2/3=40/210/940 nM) with excellent selectivity over nonclass IV BRD proteins.

GSK9311 hydrochloride, a less active analogue of GSK6853, can be used as a negative control. GSK9311 hydrochloride inhibits BRPF bromodomain with pIC₅₀ values of 6.0 and 4.3 for BRPF1 and BRPF2, respectively.

BD-IN-1 is a pan bromodomain (BD) inhibitor with K_D values of 250, 420, 130, 430, 67, 240, 970 nM for BRD4(1), CBP, BRPF1B, BRD7, BRD9, BRDT(1), CECR2 respectively. BD-IN-1 shows antiproliferative activity.

HDAC8/BRPF1-IN-1 (Compound 23a) is a dual inhibitor of HDAC8 and BRPF1 with an IC₅₀ of 443 nM against human HDAC8 and a K_d of 67 nM against human BRPF1. HDAC8/BRPF1-IN-1 shows low in vitro activity against HDAC1 and 6.

BRPF1B/TRIM24-IN-1 (compound 34) is a potent TRIM24/BRPF1/BRPF2 inhibitor, with IC₅₀ values of 0.43, 0.34, 1.75 μM, respectively. BRPF1B/TRIM24-IN-1 binds the TRIM24 bromodomain with a K_D of 222 nM and has a K_D for the BRPF1 bromodomain of 137 nM and for BRD1 of 1130 nM.