VB124
目录号 : GC63496
VB124是一种安全有效、具有口服活性的选择性单羧酸盐转运蛋白4(MCT4) 抑制剂，VB124阻断了MDA-MB-231细胞中的乳酸输入（IC50 = 8.6nM）和输出（IC50 = 19nM）。
Cas No.:2230186-18-0
Sample solution is provided at 25 µL, 10mM.
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VB124 is a safe, effective and orally active selective monocarboxylate transport protein 4(MCT4) inhibitor. VB124 blocks the input (IC50 = 8.6nM) and output (IC50 = 19nm) of lactic acid in MDA-MB-231 cells[1].
In vitro, mouse primary cardiomyocytes (ACM) subjected to hypoxia-reoxygenation were treated with VB124 to mitigate intracellular reactive oxygen species (ROS) levels and reduce cardiomyocyte apoptosis[2]. Treatment of HMCC97H and Hepa1-6 cells with VB124 (2,10μM) significantly inhibited lactic acid effusion caused by MCT4, reduced extracellular lactic acid levels, and further led to a decrease in glucose uptake and an increase in glutamine uptake[3].
In vivo, a single-dose oral administration of VB124 (30mg/kg) by gavage was used to create an acute cardiac ischemia-reperfusion model in mice. VB124 inhibited MCT4, resulting in a decrease in intracellular lactate and pyruvate levels, further exacerbating hypoxic injury caused by acute cardiac ischemia-reperfusion (I/R) in mice[2,4].
References:
[1]Cluntun AA, Badolia R, Lettlova S, Parnell KM, Shankar TS, Diakos NA, Olson KA, Taleb I, Tatum SM, Berg JA, Cunningham CN, Van Ry T, Bott AJ, Krokidi AT, Fogarty S, Skedros S, Swiatek WI, Yu X, Luo B, Merx S, Navankasattusas S, Cox JE, Ducker GS, Holland WL, McKellar SH, Rutter J, Drakos SG. The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure. Cell Metab. 2021 Mar 2;33(3):629-648.e10.
[2] Visker JR, Cluntun AA, Velasco-Silva JN, Eberhardt DR, Cedeño-Rosario L, Shankar TS, Hamouche R, Ling J, Kwak H, Hillas JY, Aist I, Tseliou E, Navankasattusas S, Chaudhuri D, Ducker GS, Drakos SG, Rutter J. Enhancing mitochondrial pyruvate metabolism ameliorates ischemic reperfusion injury in the heart. JCI Insight. 2024 Jul 25;9(17):e180906.
[3]Fang Y, Liu W, Tang Z, Ji X, Zhou Y, Song S, Tian M, Tao C, Huang R, Zhu G, Jiang X, Gao J, Qu W, Wang H, Zhou P, Wu X, Jin L, Sun H, Ding Z, Peng Y, Zhao S, Zhou J, Fan J, Xu W, Shi Y. Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack. Hepatology. 2023 Jan 1;77(1):109-123.
[4]Tuineau MN, Herbert LM, Garcia SM, Resta TC, Jernigan NL. Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2024 Oct 1;327(4):L439-L451.
VB124是一种安全有效、具有口服活性的选择性单羧酸盐转运蛋白4(MCT4) 抑制剂，VB124阻断了MDA-MB-231细胞中的乳酸输入（IC50 = 8.6nM）和输出（IC50 = 19nM）[1]。
在体外，VB124处理通过缺氧再复氧的小鼠原代心肌细胞（ACM），降低胞内活性氧（ROS）水平，减少心肌细胞死亡[2]。VB124 (2、10μM)处理HMCC97H和Hepa1-6细胞，显著抑制MCT4导致的乳酸外排，降低细胞外乳酸水平，并进一步导致葡萄糖摄取减少和谷氨酰胺摄取增加[3]。
在体内，VB124（30mg/kg）单剂量口服灌胃后对小鼠造心脏急性缺血再灌注模型，VB124通过抑制MCT4，导致胞内乳酸和丙酮酸水平降低，进一步加重小鼠急性心脏缺血再灌注（I/R）导致的缺氧损伤[2,4]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 |
Preparation Method | MCT4 and MCT1 lactate transport assays that use the pH-sensitive fluorescent dye 2′−7′-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) to detect changes in intracellular pH (pHi) accompanying MCT-mediated lactate/proton symport, were developed in a manner similar to that reported previously.To measure lactate import, 2.5μL BCECF-loaded cells, along with either 10μL DMSO or 100x compound in DMSO, were added to 937.5μL of Tyrode’s Solution in a quartz 1.0mL cuvette. Fluorescence measurements are performed on a PerkinElmer LS55 fluorescence spectrometer with dual excitation wavelengths achieved using a filter wheel. After establishing baseline BCECF fluorescence (around 10–20s), 50μL of M sodium L-lactate was added to the cuvette (final concentration: 50mM) and rapidly mixed. The time-dependent decrease in BCECF fluorescence (490/440 ratio) was fit to an exponential decay curve to determine the rate of lactate transport. Lactate export was measured similarly to import. |
Reaction Conditions | MCT4-mediated import:0-3.3μM; MCT4-mediated export:0-10μM; |
Applications | VB124 treatment reduces intracellular reactive oxygen species (ROS) levels and decreases cardiomyocyte death. |
| Animal experiment [2]: | |
Animal models | C57BL/6J |
Preparation Method | To test this, we replicated our I/R protocol administering either a single dose of placebo or VB124 (30 mg/kg) via oral gavage prior to performing I/R. Unlike in the acute model, the mice were permitted to recover after surgery, and we performed serial echocardiography over a 3-week period to assess cardiac structure and function . |
Dosage form | 30mg/kg; i.g; |
Applications | VB124 inhibits MCT4, resulting in a decrease in intracellular lactate and pyruvate levels, further exacerbating hypoxic injury caused by acute cardiac ischemia-reperfusion (I/R) in mice. |
References: | |
| Cas No. | 2230186-18-0 | SDF | |
| 分子式 | C23H23ClN2O4 | 分子量 | 426.89 |
| 溶解度 | DMSO : 100 mg/mL (234.25 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3425 mL | 11.7126 mL | 23.4252 mL |
| 5 mM | 0.4685 mL | 2.3425 mL | 4.685 mL |
| 10 mM | 0.2343 mL | 1.1713 mL | 2.3425 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Quality Control & SDS
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- Purity: >99.00%
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