I-BET567 是一种有效、具有口服活性pan-BET候选抑制剂，对 BRD4 BD1 和 BD2 的pIC50s 分别为 6.9 和 7.2。I-BET567 已在肿瘤和炎症小鼠模型中已被证明有效。
| 生物活性 | I-BET567 is a potent and orally active inhibitor ofpan-BETcandidate withpIC50s of 6.9 and 7.2 forBRD4BD1 andBD2, respectively. I-BET567 has been demonstrated efficacy in mouse models of oncology and inflammation[1]. |
| IC50& Target | BRD4 (BD1) 6.9 (pIC50) | BRD2 7.2 (pIC50) |
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体外研究
(In Vitro) | 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 gpIC506.2 (0.63 μM)[1].
Cell Viability Assay[1] | Cell Line: | NMC line 11060 cells | | Concentration: | 1.5 nM-30 μM | | Incubation Time: | 72 hours | | Result: | Significantly reduced cell growth. |
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体内研究
(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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(277.92 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.7792 mL | 13.8962 mL | 27.7924 mL | | 5 mM | 0.5558 mL | 2.7792 mL | 5.5585 mL | | 10 mM | 0.2779 mL | 1.3896 mL | 2.7792 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (protect from light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.95 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.95 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (6.95 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.95 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.95 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.95 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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