Chronologically Modified Androgen Receptor in Recurrent Castration Resistant Prostate Cancer and its therapeutic targeting

We uncovered a novel acetylation event at Lys609 in the Zinc finger DNA binding domain of AR (acK609-AR) that altered global transcription program, bestowing insensitivity for enzalutamide and abiraterone. ACK1 kinase small molecule inhibitor, (R)-9b not only curbed K609-acetylation, but also significantly compromised enzalutamide-resistant CRPC tumor growth. Overall design: Examination of binding profile of Lys609-acetylated androgen receptor (acK609-AR) in VCaP prostate cancer cells, and effect upon inhibitor R-9b treatment