GSK620

GSK620 is highly selective for the BET-BD2 family of proteins, with >200-fold selectivity over all other bromodomains. GSK620 is capable of reducing the MCP-1 response in a concentration-dependent manner, providing strong evidence that GSK620 is indeed engaging BD2 in cells.^[1]

GSK620 is diluted in 100% DMSO to give a range of appropriate concentrations at 140× the required final assay concentration, of which 1 μL is added to a 96 well tissue culture plate. Then 130 μL of human whole blood, collected into sodium heparin anticoagulant (1 unit/mL final) is added to each well and plates are incubated at 37℃ (5% CO2) for 30 min before the addition of 10 μL of 2.8 μg/mL LPS, diluted in complete RPMI 1640 (final concentration 200 ng/mL), to give a total volume of 140 μL per well. After further incubation for 24 h at 37℃, 140 μL of PBS is added to each well. The plates are sealed, shaken for 10 min, and then centrifuged (2500 rpm × 10 min). Finally, 100 μL of the supernatant is removed and MCP-1 levels assayed immediately by immunoassay.

GSK620 is a potent and selective pan-BD2 inhibitor with excellent in vivo PK properties and excellent developability properties, with the exception of moderate FaSSIF solubility driven by its highly crystalline nature.^[1]