Here we report the discovery of ABBV-744, a first in class, highly potent and selective inhibitor of BET family BD2 domains with drug like properties. RNA-seq analysis revealed that ABBV-744 elicited potent inhibition of AR-dependent transcription without causing broad transcription alterations associated with exposure to pan BET inhibitors. Overall design: mRNA profiles of 22RV1 cells treated with ABBV-075, ABBV-744, or Enzalutmide in the presence or absence of DHT were generated by deep sequencing, in duplicate, using Illumina HiSeq3000.