BL-918 是一种具有口服活性 UNC-51 样激酶 1 (ULK1) 激活剂，EC50为 24.14 nM。BL-918 通过靶向 ULK 复合物发挥其细胞保护性自噬作用。BL-918 有用于帕金森氏病 (PD) 的潜力。
| 生物活性 | BL-918 is an orally activeUNC-51-like kinase 1 (ULK1)activator with anEC50of 24.14 nM. BL-918 exerts its cytoprotectiveautophagiceffect by targetingULKcomplex. BL-918 has the potential for Parkinson’s disease (PD) treatment[1]. |
| IC50& Target[1] | ULK1 24.14 nM (EC50) | ULK1 0.719 μM (Kd) |
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体外研究
(In Vitro) | BL-918 (compound 33i) binds to ULK1 with a high binding affinity (KD=0.719 μM)[1].
BL-918 (5 μM; for 24 hours) induces autophagy in Neuron-Like SH-SY5Y cells[1].
BL-918 (0.5-50 μM; for 24 hours) can partially reverse MPP+-induced cell death, which is determined by enhancing cell viability[1].
BL-918 (5 μM; for 6-36 hours) time-dependently elevates the expression levels of LC3-II, Beclin-1, and its phosphorylation status, whereas reduces the level of the selective autophagy substrate SQSTM1/p62. BL-918 elevates Ser317 and Ser555 phosphorylation of ULK1, as well as decreases Ser757 phosphorylation of ULK1[1].
Cell Autophagy Assay[1] | Cell Line: | SH-SY5Y cells | | Concentration: | 5 μM | | Incubation Time: | For 24 hours | | Result: | Induced Autophagy. |
Cell Viability Assay[1] | Cell Line: | SH-SY5Y cells | | Concentration: | 0.5, 5, 50 μM | | Incubation Time: | For 24 hours | | Result: | Could partially reverse MPP+-induced cell death, which was determined by enhancing cell viability. |
Western Blot Analysis[1] | Cell Line: | SH-SY5Y cells | | Concentration: | 5 μM | | Incubation Time: | 6, 12, 24, 36 hours | | Result: | Time-dependently elevated the expression levels of LC3-II (a key marker of autophagy), Beclin-1, and its phosphorylation status, whereas reduced the level of the selective autophagy substrate SQSTM1/p62. |
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体内研究
(In Vivo) | BL-918 (compound 33i; 20, 40, or 80 mg/kg/day; oral gavage; began 2 days before the first injection of saline/MPTP and continuously maintained for 5 days after the last injection of saline/MPTP) attenuates the loss of DA and its metabolites. BL-918 obviously decreases the levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA)[1].
| Animal Model: | Male C57BL/6 mice (eight-week old) weighing between 20 and 25 g[1] | | Dosage: | 20, 40, or 80 mg/kg | | Administration: | Oral gavage; daily; began 2 days before the first injection of saline/MPTP and continuously maintained for 5 days after the last injection of saline/MPTP | | Result: | Attenuated the loss of DA and its metabolites. |
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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 : ≥ 250 mg/mL(468.66 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.8746 mL | 9.3731 mL | 18.7463 mL | | 5 mM | 0.3749 mL | 1.8746 mL | 3.7492 mL | | 10 mM | 0.1875 mL | 0.9373 mL | 1.8746 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: ≥ 2.08 mg/mL (3.90 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.90 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。 |
