GSK215 是一种有效且具有选择性的PROTAC粘着斑激酶(FAK)降解剂，pDC50值为 8.4。GSK215 是由 VHL E3 连接酶粘合剂和FAK 抑制剂 VS-4718 联合设计的。GSK215 诱导 FAK 快速而持久性的降解，对 FAK 水平产生长期影响，并显著降低药代动力学/药效学 (PK/PD)。
| 生物活性 | GSK215 is a potent and selectivePROTACfocal adhesion kinase (FAK)degrader with a pDC50of 8.4. GSK215 is designed by a binder for the VHL E3 ligase and theFAK inhibitorVS-4718. GSK215 induces rapid and prolongedFAKdegradation, giving a long-lasting effect onFAKlevels and a marked pharmacokinetic/pharmacodynamics (PK/PD) disconnect[1]. |
| IC50& Target | PROTAC; pDC50: 8.4 (FAK)[1] |
体外研究
(In Vitro) | GSK215 (0.1-1000 nM; 2 h) effectively increases the FAK degradation by >90% and determines a DC50of 1.3 nM in A549 cells[1].
GSK215 induced degradation is proteasome and ubiquitin dependent[1].
GSK215 (above 100 nM, 6h) reduces primarily kinases CDK7, RPS6KA3, MET and GAK[1].
GSK215 (100 nM, 48 h) inhibits migration, invasion and collagen deposition in A549 cells[1].
Western Blot Analysis[1] | Cell Line: | A549 cells | | Concentration: | 0.1-1000 nM | | Incubation Time: | 2 h | | Result: | Increased the FAK degradation. |
Cell Migration Assay[1] | Cell Line: | A549 cells | | Concentration: | 100 nM | | Incubation Time: | 48 h | | Result: | Inhibited cell migration. |
Cell Invasion Assay[1] | Cell Line: | A549 cells | | Concentration: | 100 nM | | Incubation Time: | 48 h | | Result: | Inhibited cell invasion. |
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体内研究
(In Vivo) | GSK215 (8 mg/kg; i.h.; once) degrades FAK, and shows the Cmaxand tmaxvalues of 526 ng/mL and 0.33 hours, respectively[1].
| Animal Model: | Male CD1 mice (P878/881A), 7-9 weeks[1] | | Dosage: | 8 mg/kg | | Administration: | Single subcutaneous injection | | Result: | Caused a rapid and profound degradation of FAK in liver over time, with a maximal degradation of ~85% being achieved within 18 h. Endogenous FAK was found to still be reduced by ~60% at 96 h post-dose.The Cmaxand tmaxwere 526 ng/mL and 0.33 hours, respectively. |
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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(253.77 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.0151 mL | 5.0755 mL | 10.1509 mL | | 5 mM | 0.2030 mL | 1.0151 mL | 2.0302 mL | | 10 mM | 0.1015 mL | 0.5075 mL | 1.0151 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 (2.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (2.11 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%corn oil Solubility: ≥ 2.08 mg/mL (2.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (2.11 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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