| 名称 | AZD3965 |
| 描述 | AZD3965 (AZD-3965) belongs to small molecule inhibitors, serving as a monocarboxylate transporter 1 (MCT1) inhibitor (Ki=1.6 nM), with 6-fold higher selectivity for MCT1 over MCT2, featuring favorable selectivity, cell permeability, and oral activity, for antitumor research. |
| 激酶实验 | Cells are plated overnight and treated with 100 nM AZD3965 or vehicle for 24 hours. The cells are then washed, once in PBS and twice with lysis buffer (50 mM Mops, 100 mM KCl, 5 mM MgCl2, 1 mM EDTA, 0.1 mM DTT, 1 mM PMSF supplemented with 1× mini complete protease inhibitor cocktail tablets. The cells are harvested by scraping and centrifugation, and the pellet snap frozen without buffer in liquid nitrogen. Frozen aliquots of cells are thawed on ice and re-suspended in lysis buffer. Cells are lysed by 3 rounds of freezing in liquid nitrogen and thawing at 37°C for 2 minutes each. Lysates are subsequently centrifuged (13000 g, 10min, 4°C) until clear and then stored on ice. Enzyme activity in the cell lysates is determined using a micro-plate reader to measure either production or depletion of NADH/NADPH, through its absorbance at 340/10 nm, occurring as a result of direct or coupled enzyme reactions. The 96 well plates used for the assays are pre-heated to 37°C for 10 minutes prior to starting reactions, initiated by the addition of 5 μL cell lysate to 95 μL of reaction buffer (50 mM Mops pH 7.4, 100 mM KCl, 5 mM free magnesium). The standard reaction buffer is supplemented to assay the kinetics of the different enzymes. Absorbance values for controls are subtracted from absorbance of corresponding reactions. Graphpad prism 6 is used to plot V0 values against substrate concentration and determine Vmax and Km values. The Vmax is then normalised to the protein concentration in the cell lysate[1]. |
| 体外活性 | 方法：在4T1小鼠乳腺癌细胞中，采用L-乳酸摄取实验评估AZD3965的体外活性。细胞与200 nM AZD3965预孵育不同时间，观察其对L-乳酸摄取的抑制作用；洗脱抑制剂后，监测抑制恢复情况。
结果：AZD3965呈时间依赖性抑制L-乳酸摄取，预孵育5 min后达最大抑制并持续；洗脱后抑制在12 h完全逆转，表明其抑制作用缓慢可逆。[1]
方法：在Raji人淋巴瘤细胞中，采用L-乳酸水平检测实验评估AZD3965活性。细胞与2~500 nM AZD3965孵育24 h，或与25 nM AZD3965孵育不同时间。
结果：AZD3965呈浓度依赖性增加细胞内乳酸，2 nM即有效（P=0.01P=0.01），25 nM达最大积累；时间依赖性分析显示，90 min后乳酸显著升高（P=0.02P=0.02），3 h达峰。[2] |
| 体内活性 | 方法：采用NOD/LtSz-scid IL2Ry⁰（NSG）小鼠，通过尾静脉注射荧光素酶标记的CA46细胞构建伯基特淋巴瘤模型。AZD3965以100 mg/kg剂量每日两次口服给药，连续治疗24天，对照组给予溶媒。
结果：AZD3965单药显著抑制肿瘤生长，肿瘤负荷较治疗前无显著增加，脾脏重量及骨髓浸润亦明显减少，证实其在体内具有强效抑瘤活性。[3]
方法：在BALB/c小鼠4T1三阴性乳腺癌模型中，待皮下移植瘤体积达100 mm³后，腹腔注射AZD3965（100 mg/kg，每日两次，溶于20%环糊精生理盐水，对照为溶剂），连续给药17天。
结果：AZD3965可降低肿瘤体积与增殖标志物Ki67表达，升高瘤内乳酸浓度，但未改变肿瘤重量，且肺转移结节增多。[4] |
| 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 | Ethanol : 100 mg/mL (193.98 mM), Sonication is recommended.
DMSO : 100 mg/mL (193.98 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 4 mg/mL (7.76 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 关键字 | Monocarboxylatetransporter | Monocarboxylate Transporter | MCT1 | Inhibitor | inhibit | AZD3965 |
| 相关产品 | D-Phenylalanine | Acriflavine Hydrochloride | 7ACC2 | VB124 | Syrosingopine | Niflumic acid | 7ACC1 | MSC-4381 | α-Cyano-4-hydroxycinnamic acid | MCT1-IN-3 | Coumarin343 | Acriflavine |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | NO PAINS 化合物库 | 临床前化合物库 | 血液病分子库 | 临床期小分子药物库 | 膜蛋白靶向化合物库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |
