View interactive charts of activity data from GtoPdb and ChEMBL (where available) across species
|JQ1 displaces BRD4 from nuclear chromatin in vitro, induces squamous cell differentiation and growth arrest in NUT midline carcinoma (NMC) cells and exhibits antitumour activity in xenograft models of NMC . (+)-JQ1 binds to BRD4-BD1 with a Kd of approximately 50nM and to BRD4-BD2 with a Kd of 90 nM . In male mice, (+)-JQ1 inhibits the chromatin remodelling that is essential during spermatogenesis, and has a complete and reversible contraceptive effect . Crystallographic study shows that (+)-JQ1 occupies the acetylysine binding site on BRDT, thus preventing BRDT-histone H4 interaction .
JQ1-induced inhibition of BET domain containing proteins such as BRD4, inactivates Myc oncogene activity, which in turn switches off expression of programmed death-ligand 1 (PD-L1) and CD47 . Both PD-L1 and CD47 are up-regulated in tumours under Myc control and act in concert to suppress immune detection of the cancer cells. Thus, Myc inhibition appears as a novel immuno-oncology target.