6-Quinolinecarboxamide, 1-acetyl-4-[(5-chloro-2-pyrimidinyl)amino]-1,2,3,4-tetrahydro-2-methyl-, (2S,4R)-

Biological Activity

I-BET567 is a potent and orally active inhibitor of pan-BET candidate with pIC50s of 6.9 and 7.2 for BRD4 BD1 and BD2, respectively. I-BET567 has been demonstrated efficacy in mouse models of oncology and inflammation[1]. I-BET567 (compound 27) (72 hours; 1.5 nM-30 μM) effectively inhibites the proliferation of human NMC cell line 11060 in vitro with a mean gpIC50 6.2 (0.63 μM)[1]. I-BET567 (compound 27) (3, 10, and 30 mg/kg; p.o.; once daily for 20 days) leads to a significant reduction in tumor growth compared with vehicle controls at both 10 and 30 mg/kg[1].Assessment of Pharmacokinetics (PK) profile of I-BET567 following intravenous infusion and oral administration in male wistar han rat and beagle doga[1]. species dose ivb/poc (mg/kg) CLb (mL/min/kg) CLb,u (mL/min/kg) CLrenal (mL/min/kg) Vss (L/kg) Vss,u (L/kg) t1/2 (h) Fpo (%) fub rat1.3/32510972.410.41.699d0.23 dog1.0/38.1206.91.22.91.8980.41a: Values are mean, n=3 unless otherwise stated. b: IV dose 1h infusion in DMSO and (10%, w/v) Kleptose HPB in saline (2%: 98% (v/v)). c: PO dose vehicle: 1%(w/v) methycellulose (400 cps) (aq). d: Mean n = 2.

References

[1]. Humphreys PG, et al. Design, Synthesis, and Characterization of I-BET567, a Pan-Bromodomain and Extra Terminal (BET) Bromodomain Oral Candidate [published online ahead of print, 2022 Jan 7].