I-BET567, a potent pan-BET inhibitor with oral activity, demonstrates pIC50 values of 6.9 and 7.2 for BRD4 BD1 and BD2, respectively. This compound has exhibited efficacy in mouse models of oncology and inflammation [1].

BRD2:7.2 (pIC50), BRD4 BD1:6.9 (pIC50)

I-BET567 (compound 27) significantly inhibits the in vitro proliferation of the NMC cell line 11060 with a gpIC50 of 6.2 (0.63 μM) [1] over a 72-hour treatment with concentrations ranging from 1.5 nM to 30 μM, as observed in a Cell Viability Assay [1].

I-BET567 (compound 27), administered orally at doses of 3, 10, and 30 mg/kg daily for 20 days, significantly reduced tumor growth in a NMC 11060 xenograft mouse model compared to vehicle controls at dosages of 10 and 30 mg/kg. Pharmacokinetic profiling of I-BET567, following both intravenous infusion and oral administration, was conducted in male Wistar Han rats and beagle dogs, revealing distinct pharmacokinetic parameters across species, doses, and administration routes. Notably, the oral bioavailability in rats and dogs was high, with values reaching 99% and 98%, respectively. This study elucidates the effectiveness of I-BET567 in tumor suppression and provides comprehensive pharmacokinetic data, including clearance rates, volume of distribution, and half-life across two species, which could inform future research and development efforts involving this compound.