GSK973 is a highly selective and orally bioavailable inhibitor that targets the second bromodomains (BD2s) of the BET family. It exhibits a pIC 50 of 7.8 and a pK d of 8.7 specifically for BRD4 BD2. Additionally, GSK973 demonstrates a remarkable selectivity of 1600-fold for BRD4 BD2 over BRD4 BD1. Moreover, it displays good potency against BRD2 BD2, BRD3 BD2, and BRDT BD2, with pIC 50 ranging from 7.4 to 7.8 and pK d ranging from 8.3 to 8.5.

BRD3 BD2:8.5 (pKd), BRDT BD2:8.3 (pKd), BRD2 BD2:7.5 (pIC50), BRD2 BD2:8.3 (pKd), BRD4 BD2:8.7 (pKd), BRD3 BD2:7.8 (pIC50), BRDT BD2:7.4 (pIC50), BRD4 BD2:7.8 (pIC50)

Treatment with GSK973 at a dosage of 1 mg/kg administered intravenously (i.v.) demonstrated pharmacokinetic properties in male Wistar Han rats, including a clearance (CL) of 73 mL/min/kg, a renal clearance (CI renal) of 4 mL/min/kg, a steady-state volume of distribution (V ss) of 2.1L/kg, and a half-life (T 1/2) of 0.6 hours. Additionally, when administered orally (p.o) at a dose of 3 mg/kg, GSK973 exhibited an oral bioavailability (F po) of 48%. These findings provide insights into the drug's absorption, distribution, metabolism, and excretion characteristics following different routes of administration[1].