BRD0705 是一种有效的，具有旁系选择性和口服活性的GSK3α抑制剂，IC50为 66 nM，Kd为 4.8 μM。 BRD0705 与 GSK3β (IC50为 515 nM) 相比，对GSK3α的选择性更高 (8 倍)。BRD0705 可用于急性髓细胞性白血病的研究。
| 生物活性 | BRD0705 is a potent, paralog selective and orally activeGSK3αinhibitor with anIC50of 66 nM and aKdof 4.8 μM. BRD0705 displays increased selectivity forGSK3α(8-fold) versus GSK3β (IC50of 515 nM). BRD0705 can be used for acute myeloid leukemia (AML) research[1]. |
| IC50& Target[1] | GSK3α 66 nM (IC50) | GSK3α 4.8 μM (Kd) | GSK-3β(WT) 515 nM (IC50) |
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体外研究
(In Vitro) | BRD0705 displays excellent selectivity in a penal of 311 kinases, the CDK family of kinases (CDK2, 3 and 5) are next most potently inhibits at values of 6.87 μM, 9.74 μM and 9.20 μM (87-fold, 123-fold and 116-fold selectivity relative to GSK3α)[1].
BRD0705 (10-40 μM; 2-24 hours; U937 cells) treatment impairs GSK3α Tyr279 phosphorylation in a time-and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation[1].
Using a β-catenin dependent TCF/LEF luciferase reporter assay, the absence of β-catenin induced target activation after treatment with BRD0705 in AML cell lines[1].
BRD0705 impairs AML colony formation in all six tested cell lines, MOLM13, TF-1, U937, MV4-11, HL-60 and NB4, in a concentration-dependent manner, as opposed to BRD3731 which impairs colony formation in TF-1 while increasing colony forming ability in the MV4-11 cell line[1].
Western Blot Analysis[1] | Cell Line: | U937 cells | | Concentration: | 10 μM, 20 μM and 40 μM | | Incubation Time: | 2 hours, 4 hours, 8 hours and 24 hours | | Result: | Impaired GSK3α Tyr279 phosphorylation in a time-and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation. |
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体内研究
(In Vivo) | BRD0705 (30 mg/kg; oral gavage; twice daily; NSG mice) treatment impairs leukemia initiation and prolongs survival in AML mouse models[1].
| Animal Model: | 8-week-old male NSG mice injected with MLL-AF9 AML cells[1] | | Dosage: | 30 mg/kg | | Administration: | Oral gavage; twice daily | | Result: | Mice survival was significantly improved. |
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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 : 300 mg/mL(933.36 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1112 mL | 15.5560 mL | 31.1119 mL | | 5 mM | 0.6222 mL | 3.1112 mL | 6.2224 mL | | 10 mM | 0.3111 mL | 1.5556 mL | 3.1112 mL |
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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
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此方案可获得 ≥ 7.5 mg/mL (23.33 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 75.0 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%corn oil Solubility: ≥ 7.5 mg/mL (23.33 mM); Clear solution
此方案可获得 ≥ 7.5 mg/mL (23.33 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 75.0 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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