BET bromodomain inhibitor 1 是一种具有口服活性的，选择性BET溴结构域抑制剂，对 BRD4 的IC50为 2.6 nM。BET bromodomain inhibitor 1 与 BRD2(2)，BRD3(2)，BRD4(1)，BRD4(2) 和 BRDT(2) 高亲和力结合 (Kd值分别为 1.3 nM、1.0 nM、3.0 nM、1.6 nM、2.1 nM)。BET bromodomain inhibitor 1 具有抗癌活性。
| 生物活性 | BET bromodomain inhibitor 1 is an orally active, selectivebromodomain and extra-terminal (BET) bromodomaininhibitor with anIC50of 2.6 nM forBRD4. BET bromodomain inhibitor 1 binds to BRD2(2), BRD3(2), BRD4(1), BRD4(2), and BRDT(2) with high affinities (Kdvalues of 1.3 nM, 1.0 nM, 3.0 nM, 1.6 nM, 2.1 nM, respectively). bromodomain inhibitor 1 has anti-cancer activity[1]. |
| IC50& Target[1] | BRD4 2.6 nM (IC50) | BRD2(2) 1.3 nM (Kd) | BRD3(2) 1.0 nM (Kd) | BRD4(1) 3.0 nM (Kd) | BRD4(2) 1.6 nM (Kd) | BRDT(2) 2.1 nM (Kd) |
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体外研究
(In Vitro) | BET bromodomain inhibitor 1 (compound 38; 31.25-125 nM; 24 hours) leads to more pronounced G1-phase cell cycle arrest[1].
BET bromodomain inhibitor 1 (31.25-500 nM; 6 or 24 hours) is highly effective in inducing dose-dependent inhibition on c-Myc expression and upregulation of p21 levels[1].
BET bromodomain inhibitor 1 (31.25-125 nM; 6 hours) robustly reduces the expressions of c-Myc, BCL-2, and CDK6[1].
BET bromodomain inhibitor 1 does not inhibit five cytochrome P450 enzymes (IC50>20 μM)[1].
BET bromodomain inhibitor 1 demonstrates an excellent selectivity for the BET bromodomain family over other bromodomains, with an ~1500-fold selectivity for BRD4(1) over EP300 (IC50=3857 nM)[1].
BET bromodomain inhibitor 1 strongly inhibited the growth of acute myeloid leukemia cell line MV4-11, acute leukemia cell lines Kasumi-1 and RS-4-11, and multiple myeloma cancer cell line MM1.S cells with IC50values of 2.4, 4.8, 17.6 and 15.1 nM, respectively[1].
Cell Cycle Analysis[1] | Cell Line: | MV-4-11 cells | | Concentration: | 31.25, 62.5, 125 nM | | Incubation Time: | 24 hours | | Result: | Led to more pronounced G1-phase cell cycle arrest. |
Western Blot Analysis[1] | Cell Line: | MV-4-11 cells | | Concentration: | 31.25, 62.5, 125, 250, 500 nM | | Incubation Time: | 6 or 24 hours | | Result: | Induced dose-dependent inhibition on c-Myc expression and upregulation of p21 levels. |
RT-PCR[1] | Cell Line: | MV-4-11 cells | | Concentration: | 31.25, 62.5, 125 nM | | Incubation Time: | 6 hours | | Result: | Robustly reduced the expressions of c-Myc, BCL-2, and CDK6. |
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体内研究
(In Vivo) | BET bromodomain inhibitor 1 (compound 38; 6.25, 12.5 mg/kg; PO; daily ; for 28 days) exhibits stronger antitumor activities and completely inhibits the growth of tumor with a tumor growth inhibition (TGI) of 99.7% at 12.5 mg/kg[1].
BET bromodomain inhibitor 1 (1 mg/kg; IV) has a T1/2of 1.3 and 0.9 hours, a CL of 21.5 and 15.3 mL/minokg, and a Vssof 1464 and 782 mL/kg for rats and mouse, respectively[1].
BET bromodomain inhibitor 1 (3 mg/kg; PO) has a T1/2of 3.6 hours, a Cmaxof 159 ng/mL and an AUC of 884 ngoh/mL for rats[1].
BET bromodomain inhibitor 1 (1.3 mg/kg; PO) has a T1/2of 1.3 hours, a Cmaxof 399 ng/mL and an AUC of 1710 ngoh/mL for mouse[1].
| Animal Model: | An MV4-11 mouse xenograft model[1] | | Dosage: | 6.25, 12.5 mg/kg | | Administration: | PO; daily ; for 28 days | | Result: | Exhibited stronger antitumor activities and completely inhibited the growth of tumor with a tumor growth inhibition (TGI) of 99.7% at 12.5 mg/kg. |
| Animal Model: | Male SD rats[1] | | Dosage: | 1 mg/kg (Pharmacokinetic Analysis) | | Administration: | IV | | Result: | Had a T1/2of 1.3 hours, a CL of 21.5 mL/minokg, and a Vssof 1464 mL/kg. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 62.5 mg/mL(136.03 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 2.1764 mL | 10.8821 mL | 21.7642 mL | | 5 mM | 0.4353 mL | 2.1764 mL | 4.3528 mL | | 10 mM | 0.2176 mL | 1.0882 mL | 2.1764 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。-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 90%corn oil Solubility: ≥ 2.5 mg/mL (5.44 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.44 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。 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.53 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 3. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.53 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 *以上所有助溶剂都可在本网站选购。
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