I-BET567

• CAT Number: I045210
• CAS Number: 1887237-54-8
• Molecular Formula: C17H18ClN5O2
• Molecular Weight: 359.81
• Purity: ≥95%
• Synonyms: (2S,4R)-1-acetyl-4-[(5-chloropyrimidin-2-yl)amino]-2-methyl-3,4-dihydro-2H-quinoline-6-carboxamide
• InChI: InChI=1S/C17H18ClN5O2/c1-9-5-14(22-17-20-7-12(18)8-21-17)13-6-11(16(19)25)3-4-15(13)23(9)10(2)24/h3-4,6-9,14H,5H2,1-2H3,(H2,19,25)(H,20,21,22)/t9-,14+/m0/s1
• InChIKey: KNBYFXZNSOENGW-LKFCYVNXSA-N
• SMILES: CC1CC(C2=C(N1C(=O)C)C=CC(=C2)C(=O)N)NC3=NC=C(C=N3)Cl

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

rat
1.3/3
25
109
7
2.4
10.4
1.6
99d
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.

Reference

[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].
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