GSK046 (iBET-BD2) 是一种有效，选择性和具有口服活性的BET蛋白BD2溴结构域的抑制剂，IC50值为 264 nM (BRD2 BD2)，98 nM (BRD3 BD2)，49 nM (BRD4 BD2) 和 214 nM (BRDT BD2)。GSK046 具有免疫调节活性。
| 生物活性 | GSK046 (iBET-BD2) is a potent, selective and orally activeBD2bromodomaininhibitor of theBETproteins, withIC50s of 264 nM (BRD2BD2), 98 nM (BRD3BD2), 49 nM (BRD4BD2) and 214 nM (BRDTBD2), respectively. GSK046 has immunomodulatory activity[1]. |
| IC50& Target[1] | BRD2 BD2 264 nM (IC50) | BRD3 BD2 98 nM (IC50) | BRD4 BD2 49 nM (IC50) | BRDT BD2 214 nM (IC50) |
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体外研究
(In Vitro) | GSK046 (1000 nM; refresh every three days) reduces the recruitment of BET proteins to interferon (IFN) target genes following IFN-γ stimulation. GSK046 appears to more prominently affect the recruitment of BRD2 and BRD3 compared to BRD4[1].
GSK046 (0.1-10 μM) displays a more selective phenotypic fingerprint, particularly inhibiting the production of key pro-inflammatory mediators including Th17 cytokines in the B and T cell co-culture system[1].
GSK046 (0.01-10 μM; 72 hours) does not affect the proliferative activity of human primary CD4+T cells but still inhibits the production of effector cytokines including IFNγ, IL-17A and IL-22[1].
GSK046 (0.005-10 μM; 48 hours) impairs macrophage activation following PMA stimulation, without impacting cellular viability[1].
Cell Proliferation Assay[1] | Cell Line: | Human primary CD4+T cell | | Concentration: | 0.001, 0.01, 0.1, 1, 10 μM | | Incubation Time: | 72 hours | | Result: | Did not affect the proliferative activity of the cells but still inhibited the production of effector cytokines. |
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体内研究
(In Vivo) | GSK046 (40 mg/kg/QD; s.c. for 14 days) has immunomodulatory activity[1].
GSK046 exhibits Cmax(C57BL6 1589, C57B16 2993 ng/mL) and terminal elimination half-lives (C57BL6 1.8, C57B16 1.9 h) following oral administration (C57BL6 10, C57B16 40 mg/kg)[1].
GSK046 exhibits Cmax(mouse 1589, rat 202 ng/mL) and terminal elimination half-lives (mouse 1.8, rat 1.4 h) following oral administration (mouse 10, rat 10 mg/kg)[1].
| Animal Model: | Male C57BL/6 mice (8/10-weeks-old) are injected with keyhole limpet hemocyanin (KLH)[1] | | Dosage: | 40 mg/kg/QD | | Administration: | S.c. injections for 14 days | | Result: | Reduced the production of anti-keyhole limpet hemocyanin (KLH) IgM and was well tolerated. |
| Animal Model: | Female C57BL/6 mice[1] | | Dosage: | 10 mg/kg (Pharmacokinetic Analysis) | | Administration: | Oral administration | | Result: | Cmax(1859 ng/mL), T1/2(1.8 h). |
| Animal Model: | Male C57BL/6 mice[1] | | Dosage: | 40 mg/kg (Pharmacokinetic Analysis) | | Administration: | Oral administration | | Result: | Cmax(2993 ng/mL), T1/2(1.9 h). |
| Animal Model: | Female Lewis rat[1] | | Dosage: | 10 mg/kg (Pharmacokinetic Analysis) | | Administration: | Oral administration | | Result: | Cmax(202 ng/mL), T1/2(1.4 h). |
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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 : 83.33 mg/mL(201.05 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.4127 mL | 12.0636 mL | 24.1272 mL | | 5 mM | 0.4825 mL | 2.4127 mL | 4.8254 mL | | 10 mM | 0.2413 mL | 1.2064 mL | 2.4127 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 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (5.02 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.02 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (5.02 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.02 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.02 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.02 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 20.8 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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