NI-57

IC50: 3.1 nM (BRPF1), 46 nM (BRPF2 (BRD1)), 140 nM (BRPF3)

NI-57 is an inhibitor of bromodomain and plant homeodomain finger-containing (BRPF), with IC ₅₀ s of 3.1, 46 and 140 nM for BRPF1, BRPF2 (BRD1) and BRPF3, respectively. NI-57 binds the BRD of BRPF1 with a K _d of 31 ± 2 nM, BRD1 with a K _d of 110 ± 13 nM, and BRPF3 with a K _d of 410 ± 47 nM, whereas binding to BRD9 is weaker (K _d 1000 ± 130 nM) measured by isothermal titration calorimetry. NI-57 shows less active effect on BRD9 (IC ₅₀ , 520 nM) and BRD4 (BD1) (IC ₅₀ , 3700 nM), TRIM24 (IC ₅₀ , 1600 nM). NI-57 also inhibits BRPF BRDs in the nucleus, but shows little effect on the proliferation of many cancer cell lines with GI ₅₀ s of 10.4 μM (NCI-H1703 cells), 14.7 μM (DMS114), 15.6 μM (HRA-19), and 16.6 μM (RERF-LC-Sq1). Furthermore, Inhibition on BRPF1 of NI-57 (10 μM) reduces the gene expression of CCL-22 by 27.7 ± 9.4%.

NI-57 has favorable oral bioavailability in mice.