I-BET567 (C09-1140-087)

I-BET567 is a potent and orally active inhibitor of pan-BET candidate with pIC 50 s of 6.9 and 7.2 for BRD4 BD1 and BD2 , respectively. I-BET567 has been demonstrated efficacy in mouse models of oncology and inflammationIn VitroI-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 gpIC 50 6.2 (0.63 μM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: NMC line 11060 cells Concentration: 1.5 nM-30 μM Incubation Time: 72 hours Result: Significantly reduced cell growth.In VivoI-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 . Assessment of Pharmacokinetics (PK) profile of I-BET567 following intravenous infusion and oral administration in male wistar han rat and beagle dog a . species dose iv b /po c (mg/kg) CL b (mL/min/kg) CL b,u (mL/min/kg) CL renal (mL/min/kg) V ss (L/kg) V ss,u (L/kg) t 1/2 (h) Fpo (%) f ub rat 1.3/3 25 109 7 2.4 10.4 1.6 99 d 0.23 dog 1.0/3 8.1 20 6.9 1.2 2.9 1.8 98 0.41 a: 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NMC 11060 xenograft mouse model (NOD/SCID mouse; bearing NMC 11060 cells) Dosage: 3, 10, and 30 mg/kg Administration: p.o. (once daily for 20 days Result: Led to a significant reduction in tumor growth compared to vehicle controls at both 10 and 30 mg/kg.Form:SolidIC50& Target:BRD4 (BD1) 6.9 (pIC 50 ) BRD2 7.2 (pIC 50 ). Specification: 0.99 Molecular Formula: C17H18ClN5O2 Molecular Weight: 359.81