LP99

LP99, an epigenetic probe, is a potent and selective inhibitor of the BRD7 and BRD9 bromodomains with a K_d of 99 nM against BRD9. LP99 disrupts the binding of BRD7 and BRD9 to chromatin in cells^[1]. IC50 & Target: Kd: 99 nM (BRD9)^[1] In Vitro: LP99 disrupts BRD9 interactions with chromatin at a concentration of 0.8 μM. BRD7- and BRD9-NanoLuc luciferase fusion proteins and fluorescently labelled histone H3.3- and H4-HaloTag fusions were expressed in HEK293 cells. The addition of LP99 decreased BRET for both BRD7 and BRD9 in both the H3.3 and H4 systems in a dose-dependent manner, with cellular IC₅₀ values in the low micromolar range for both histone. Cytotoxicity tests in U2OS cells for 24 and 72 hours shows the inhibitor to be non-toxic at concentrations of <33 μM. LP99 inhibits IL-6 secretion from THP-1 cells in a dose-dependent manner^[1].