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NI-42 is an inhibitor of the bromodomain and PHD finger-containing 1 (BRPF1) bromodomain (IC₅₀ = 7.9 nM). It is selective for BRPF1 over BRPF2/BRD1, BRPF3, BRD9, and BRD4/BD1 (IC₅₀s = 48, 260, 310, and 4,500 nM, respectively). NI-42 inhibits the growth of OCI-AML2, Nomo-1, THP-1, KG-1, and MV-4-11 acute myeloid leukemia (AML) cells (GI₅₀s = 1.3, 4.6, 5.7, 7, and 9.9 μM, respectively) and a variety of non-AML cells (GI₅₀s = 1-10 μM). It also inhibits the growth of DMS114 lung, HRA-19 colon, and RERF-LC-Sq1 lung cancer cells (GI₅₀s = 16.6, 15.6, and 17.1 μM, respectively) but not NCI H1703 lung cancer cells (GI₅₀ = >30 μM).

NI-42 is a new chemical probe for the BRPFs (bromodomain and PHD finger-containing) suitable for cellular and invivo studies to explore the fundamental biology of these proteins.

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)

[1] NIALL IGOE. 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]. Journal of Medicinal Chemistry, 2017, 60 2: 668-680. DOI: 10.1021/acs.jmedchem.6b01583
[2] NIALL IGOE. Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins[J]. Journal of Medicinal Chemistry, 2017, 60 16: 6998-7011. DOI: 10.1021/acs.jmedchem.7b00611