| 名称 | PND-1186 |
| 描述 | PND-1186 (VS-4718) is a small molecule inhibitor, a highly specific, reversible FAK inhibitor (IC50=1.5 nM) with good selectivity and cell permeability. This compound inhibits FAK phosphorylation, blocking tumor cell survival, proliferation, migration, and angiogenesis, and is primarily used for anti-tumor research on solid tumors. |
| 细胞实验 | For soft agar assays, 48-well plates are coated with a 1:4 mix of 2% agar (EM Science) in 0.2 mL growth media (bottom layer). 5×104 cells are plated per well (in triplicate) in a mixture of 0.3% agar in 0.2 mL growth media (top layer). After agar solidification, 0.2 mL growth media is added containing DMSO or PND-1186 (final concentration for 0.6 mL). In separate experiments, PND-1186 is added after 4 days. After 10 days, colonies are imaged in phase contrast, enumerated by counting 9 fields (3 fields per well), and total area determined using Image J. For all analyses, experimental points are performed in triplicate and repeated at least two times. (Only for Reference) |
| 激酶实验 | In vitro kinase activity: GST-FAK in vitro kinase activity is measured and compared to His-tagged FAK 411–686 using the K-LISA screening kit and poly(Glu:Tyr) (4:1) copolymer as a substrate immobilized on microtiter plates. IC50 values are determined with various concentrations of test compounds in a buffer containing 50 μM ATP and 10 mM MnCl2, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Na orthovanadate for 5 min at room temperature. Serial diluted compounds are tested in triplicate. Substrate phosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies with spetrophotometric color quantitation. IC50 values are determined using the Hill-Slope Model. Kinase selectivity profiling is performed by using the KinaseProfiler service. |
| 体外活性 | 方法：在多种MPM细胞（MSTO-211H、H28、Ren、1157等）及非MPM细胞中，采用AlamarBlue增殖实验检测梯度浓度PND-1186处理72 h后的IC50。
结果：CDH1 mRNA高表达的MPM细胞（如Ren、1157）对PND-1186耐药（IC50达7.20–24.86 μM），而低表达者敏感（IC50 0.70–1.20 μM）；流式细胞周期分析证实PND-1186诱导G2/M期阻滞。[1]
方法：在高糖诱导的H9c2及原代心肌细胞中，采用MTT法确定PND-1186安全剂量（5、10 μM），预处理1 h后联合高糖刺激24–48 h。
结果：PND-1186显著抑制纤维化（Col-1、TGF-β）、肥大（β-Myhc）及炎症因子（TNF-α、IL-6、IL-1β）表达，并阻断NF-κB活化。[2] |
| 体内活性 | 方法：在STZ诱导的1型糖尿病小鼠模型中，PND-1186以50 mg/kg剂量溶于0.5%羧甲基纤维素钠缓冲液，每两天口服一次，从糖尿病确诊后第9周起连续治疗8周。
结果：PND-1186有效抑制心脏FAK磷酸化，减轻心肌纤维化与肥大，改善射血分数和短轴缩短率，并降低炎症因子表达及NF-κB活化。[3] |
| 存储条件 | Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (3.99 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 34 mg/mL (67.8 mM), Sonication is recommended.
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| 关键字 | VS4718 | VS 4718 | tumor | survival | SR2516 | SR 2516 | PTK2 protein tyrosine kinase 2 | PTK2 | PND-1186 | integrin | Inhibitor | inhibit | growth | Focal adhesion kinase | FAK | cell | Apoptosis |
| 相关产品 | Formamide | Urea | Sodium Molybdate | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Tamoxifen |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 抗癌化合物库 | 已知活性化合物库 | ReFRAME 相关化合物库 | 激酶抑制剂库 | 膜蛋白靶向化合物库 | 药物功能重定位化合物库 | 酪氨酸激酶分子库 | 抗癌临床化合物库 | 抗癌药物库 |