GSK6853 is a potent, soluble, cell-active, and highly selective inhibitor of the BRPF1 bromodomain.

Screening GSK6853 against a panel of 48 unrelated assays reveals only off-target activities that are relatively weak compared to the BRPF1 potency. However, to minimize the chance of off-target effects , the recommended concentration is no higher than 1 μM in cell-based assays[1].

In male CD1 mouse, following IV administration (1 mg/kg), GSK6853 demonstrates a high blood clearance of 107 mL/min/kg, a moderate volume of distribution (5.5 L/kg) and a moderate terminal half-life of 1.7 h. Oral administration (PO, 3 mg/kg) achieves a moderate systemic exposure, with a Cmax of 42 ng/mL and Tmax of 1.5 h, resulting in a bioavailability of 22%. The intraperitoneal route of administration (IP, 3 mg/kg) reaches a Cmax of 469 ng/mL and Tmax of 0.25 h, resulting in a bioavailability of 85%. The results indicate that the IP route of administration would be suitable for dosing this molecule in potential PKPD models[1].