Extended Data Fig. 3: ABBV-744 mimics enzalutamide and ABBV-075 to block AR-dependent transcription.
From: Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer
a, Comparison of differentially regulated genes from this study with those reported in the literature using JQ1 and iBET. b, Reduction in MYC and KLK2 protein levels detected by western blot after treatment for 24 h with ABBV-075 (60 nM) or ABBV-744 (90 nM); no effect on AR was found. ABBV-075 but not ABBV-744 increases HEXIM1 protein levels. Representative of n = 3 independent experiments with similar results. For gel source data, see Supplementary Fig. 2. c, Biochemical, biophysical and cellular characteristics of the BD1 inhibitor (BD1i) described in the indicated GSK patent application. Bottom, Expression of KLK2 and MYC in LNCaP cells after 6 h treatment with ABBV-075 (60 nM), ABBV-744 (90 nM), BD1i (200 nM) or ABBV-744 (90 nM) and BD1i (200 nM) was determined by qPCR. Data are mean ± s.d. (n = 3 biologically independent samples) and are representative of n = 2 independent experiments. d, Gene set enrichment analysis of RNA-seq data (n = 2) from LNCaP cells treated with ABBV-075, ABBV-744 or enzalutamide. Statistical significance was determined using a false-discovery rate (FDR) (Benjamini–Hochberg correction) and negative enrichment scores (NES) with q < 0.05 are listed in the table. Venn diagram shows the overlap of enriched hallmarks with each treatment. AR, MYC and E2F gene set enrichment analyses are shown as examples.
