GSK778 (iBET-BD1) 是一种有效和选择性的BET蛋白BD1溴结构域的抑制剂，IC50值为 75 nM (BRD2 BD1)，41 nM (BRD3 BD1)，41 nM (BRD4 BD1) 和143 nM (BRDT BD1)。GSK778 表型化了 pan-BET抑制剂在癌症模型中的作用。
| 生物活性 | GSK778 (iBET-BD1) is a potent and selectiveBD1bromodomaininhibitor of the BET proteins, withIC50s of 75 nM (BRD2BD1), 41 nM (BRD3BD1), 41 nM (BRD4BD1), and 143 nM (BRDTBD1), respectively. GSK778 phenocopies the effects of pan-BETinhibitors incancermodels[1]. |
| IC50& Target[1] | BRD2 BD1 75 nM (IC50) | BRD3 BD1 41 nM (IC50) | BRD4 BD1 41 nM (IC50) | BRDT BD1 143 nM (IC50) |
|
体外研究
(In Vitro) | GSK778 inhibits BRD BD2 with the IC50s of 3950 nM (BRD2 BD2), 1210 nM (BRD3 BD2), 5843 nM (BRD4 BD2), and 17451 nM (BRDT BD2), respectively[1].
GSK778 (0.01-10 μM; 72 hours) inhibits the proliferative activity of human primary CD4+T cells and the production of effector cytokines including IFNγ, IL-17A and IL-22[1].
GSK778 (0.001-10 μM; 5 days) has a more pronounced effect on the growth and viability of MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells[1].
GSK778 (1000 nM; 72 hours) inhibits proliferation, induces a cell cycle arrest and apoptosis in MV4-11, MOLM13, MDA-MB-231 and MB453 cells[1].
GSK778 (1000 nM; 12 days) reduces the clonogenic capacity of primary human AML cells[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: | Inhibited the proliferative activity of the cells and the production of effector cytokines. |
Cell Viability Assay[1] | Cell Line: | MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells | | Concentration: | 0.001, 0.01, 0.1, 1, 10 μM | | Incubation Time: | 5 days | | Result: | Inhibited the growth and viability of human cancer cell lines. |
Apoptosis Analysis[1] | Cell Line: | MV4-11, MOLM13, MDA-MB-231 and MB453 cells | | Concentration: | 1000 nM | | Incubation Time: | 72 hours | | Result: | Inhibited cell proliferation and induced a cell cycle arrest and apoptosis. |
|
体内研究
(In Vivo) | GSK778 (15 mg/kg/BID; i.p. for 30 days) offers a superior survival advantage to iBET-BD2 in the aggressive MLL-AF9 AML model[1].
GSK778 (15 mg/kg/BID; s.c. for 14 days) reduces the production of anti-keyhole limpet hemocyanin (KLH) IgM and is well tolerated[1].
GSK778 exhibits Cmax(85 ng/mL), Tmax(1.48 h) and AUC∞(132 ng.h/mL) following oral administration (10 mg/kg) in mice[1].
| Animal Model: | 6-8 weeks female C57BL/6 mice are injected with MLL-AF9 cells[1] | | Dosage: | 15 mg/kg/BID | | Administration: | I.p. injections for 30 days | | Result: | Increased the survival rate of leukemia mice. |
| Animal Model: | Male CD1 mice[1] | | Dosage: | 10 mg/kg (Pharmacokinetic Analysis) | | Administration: | P.o. administration | | Result: | Cmax(85 ng/mL), Tmax(1.48 h); AUC∞(132 ng.h/mL). |
|
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 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 |
|
| 溶解性数据 | In Vitro: DMSO : 41.67 mg/mL(81.45 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9546 mL | 9.7731 mL | 19.5461 mL | | 5 mM | 0.3909 mL | 1.9546 mL | 3.9092 mL | | 10 mM | 0.1955 mL | 0.9773 mL | 1.9546 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 (4.07 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.07 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 (4.07 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (4.07 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 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 (4.07 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.07 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。
|
m.cnreagent.com