GSK547 (GSK'547) 是一种高效的选择性receptor-interacting serine/threonine protein kinase 1 (RIPK1)抑制剂，可抑制巨噬细胞介导的胰腺癌适应性免疫耐受。
| 生物活性 | GSK547 (GSK'547) is a highly selective and potent inhibitor ofreceptor-interacting serine/threonine protein kinase 1 (RIPK1), inhibits macrophage-mediated adaptive immune tolerance in pancreaticcancer[1]. |
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体外研究
(In Vitro) | GSK547 (0.1-100000 nM; 24 hours) pretreats L929 cells with recombinant TNFα and zVAD at various doses for 30 min, then cell death is induced with an IC50of 32 nM after 24 hours[1].
GSK547 up-regulates STAT1 signaling in bone marrow-derived macrophages (BMDM)[1].
Cell Viability Assay[1] | Cell Line: | L929 cells (Mouse L-cells NCTC 929) | | Concentration: | 0.1 nM; 10 nM; 1000 nM; 100000 nM | | Incubation Time: | 24 hours | | Result: | Reduced viability of L929 cells after co-treatment with TNFα and zVAD with an IC50of 32 nM. |
Western Blot Analysis[1] | Cell Line: | Bone marrow-derived macrophages (BMDM) | | Concentration: | | | Incubation Time: | 30 minutes | | Result: | Up-regulated STAT1 signaling in BMDM. |
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体内研究
(In Vivo) | GSK547 (GSK′547; RIP1i) robustly targets RIP1 in vivo. RIP1 inhibition results in immunogenic macrophage differentiation in pancreatic cancer, leading to adaptive immune activation and tumor protection for pancreatic ductal adenocarcinoma (PDA)[1].
GSK547 (100 mg/kg/day; fed via food-based dosing; 15-50 days) reduces tumor burden and extends survival compared with mice treated with controls or Nec-1s[1].
| Animal Model: | The wild-type (WT) mice orthotopically implanted withPdx1Cre;KrasG12D;Trp53R172H(KPC)-derived tumor cells[1] | | Dosage: | ~100 mg/kg | | Administration: | Fed via food-based dosing, daily, 15-50 days | | Result: | Reduced tumor burden and extended survival. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 250 mg/mL(630.69 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.5228 mL | 12.6138 mL | 25.2277 mL | | 5 mM | 0.5046 mL | 2.5228 mL | 5.0455 mL | | 10 mM | 0.2523 mL | 1.2614 mL | 2.5228 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 (stored under nitrogen)。-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： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (6.31 mM); Clear solution 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.25 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。 3. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.25 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。 4. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.25 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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