gsk4028

Description: GSK4028 is the enantiomeric isomer and a negative control of GSK4027, which is a PCAF/GCN5 bromodomain chemical probe, the pIC50 of GSK4028 is 4.9 in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and >=18000-fold selectivity over the BET family, together with >=70-fold selectivity over the wider bromodomain families.

References: J Med Chem. 2017 Jan 26; 60(2):695-709.