| Identification | Back Directory | [Name]
6-Quinolinecarboxamide, 1-acetyl-4-[(5-chloro-2-pyrimidinyl)amino]-1,2,3,4-tetrahydro-2-methyl-, (2S,4R)- | [CAS]
1887237-54-8 | [Synonyms]
I-BET567
6-Quinolinecarboxamide, 1-acetyl-4-[(5-chloro-2-pyrimidinyl)amino]-1,2,3,4-tetrahydro-2-methyl-, (2S,4R)- | [Molecular Formula]
C17H18ClN5O2 | [MOL File]
1887237-54-8.mol | [Molecular Weight]
359.81 |
| Chemical Properties | Back Directory | [Boiling point ]
631.2±65.0 °C(Predicted) | [density ]
1.380±0.06 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light | [solubility ]
DMSO : 100 mg/mL (277.92 mM; Need ultrasonic) | [form ]
Solid | [pka]
15.73±0.60(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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]. | [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. | [in vivo]
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.
| Animal Model: | NMC 11060 xenograft mouse model (NOD/SCID mouse; bearing NMC 11060 cells) [1] | | 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.
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| [IC 50]
BRD4 (BD1): 6.9 (pIC50); BRD2: 7.2 (pIC50) | [storage]
4°C, protect from light | [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]. |
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