3-Bromopyruvic acid
(Synonyms: 3-溴丙酮酸; Bromopyruvic acid; Hexokinase II Inhibitor II, 3-BP) 目录号 : GC15523
3-Bromopyruvic acid是一种抗肿瘤剂，能够抑制有氧糖酵解和氧化磷酸化过程，对丙酮酸脱氢酶（PDH）和异柠檬酸脱氢酶（IDH）的IC50值分别为15μM和35μM。
Cas No.:1113-59-3
Sample solution is provided at 25 µL, 10mM.
3-Bromopyruvic acid is an antitumor agent able to inhibit aerobic glycolysis and oxidative phosphorylation, with IC50 values of 15 and 35μM for pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH), respectively[1]. 3-Bromopyruvic acid covalently modifies hexokinase II (HEK II) and the dissociation of HEK II from mitochondria [2]. In the model of malignant tumor cells, 3-Bromopyruvic acid is used as an inhibitor of ATPase activity, which reduces ATP levels and counteracts drug efflux by acting on ATP-binding cassette transporters to reverse chemotherapy resistance[3].
In vitro, 3-Bromopyruvic acid treatment at a concentration of 25μg/ml for 48 hours led to the appearance of typical apoptotic morphological features in MCF-7 cells, including nuclear shrinkage, excessive cytoplasmic granules, and significant reductions in the expression of Bcl-2, c-Myc, and mutant p53[4]. Treatment with 3-Bromopyruvic acid (40μM) for 2 hours led to a significant decrease in the viability of U118 glioblastoma cells, and an increase in reactive oxygen species (ROS) produced in the mitochondria[5]. Treatment with 100μM 3-Bromopyruvic acid for 12 hours induced DNA breaks in THP-1 cells, thereby triggering phosphorylation of H2A.X[6].
In vivo, 3-Bromopyruvic acid treatment via intraperitoneal injection (20mg/kg; every other day for 30 days) significantly reduced tumor growth in the pancreatic cancer model of mice, prolonged the survival time of mice, led to a significant decrease in the number of myeloid suppressor cells in tumor tissues, and increased the infiltration of CD8+ T cells[7]. Intraperitoneal injection of 3-Bromopyruvic acid (8mg/kg), every 4 days, for 28 consecutive days, significantly inhibited tumor progression in the SW480 cell-xenograft mouse model, resulting in disordered vascular distribution in the tumor tissue, shrinkage of cell nuclei, and infiltration of inflammatory cells[8].
References:
[1] Jardim-Messeder D, Moreira-Pacheco F. 3-Bromopyruvic acid inhibits tricarboxylic acid cycle and glutaminolysis in HepG2 cells[J]. Anticancer research, 2016, 36(5): 2233-2241.
[2] Chen Z, Zhang H, Lu W, et al. Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate[J]. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 2009, 1787(5): 553-560.
[3] Shoshan M C. 3-Bromopyruvate: targets and outcomes[J]. Journal of bioenergetics and biomembranes, 2012, 44(1): 7-15.
[4] Liu X, Zheng X, Wang Y. Inhibitive effect of 3-bromopyruvic acid on human breast cancer MCF-7 cells involves cell cycle arrest and apoptotic induction[J]. Chinese medical journal, 2009, 122(14): 1681-1685.
[5] Petricciuolo M, Davidescu M, Fettucciari K, et al. The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells[J]. Heliyon, 2020, 6(12).
[6] Cal M, Matyjaszczyk I, Litwin I, et al. The anticancer drug 3-bromopyruvate induces DNA damage potentially through reactive oxygen species in yeast and in human cancer cells[J]. Cells, 2020, 9(5): 1161.
[7] Roy S, Dukic T, Bhandary B, et al. 3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model[J]. American Journal of Cancer Research, 2022, 12(11): 4977.
[8] Sun Y, Liu Z, Zou X, et al. Mechanisms underlying 3-bromopyruvate-induced cell death in colon cancer[J]. Journal of bioenergetics and biomembranes, 2015, 47(4): 319-329.
3-Bromopyruvic acid是一种抗肿瘤剂，能够抑制有氧糖酵解和氧化磷酸化过程，对丙酮酸脱氢酶（PDH）和异柠檬酸脱氢酶（IDH）的IC50值分别为15μM和35μM[1]。3-Bromopyruvic acid通过共价修饰己糖激酶II（HK II）并促使HK II从线粒体解离发挥作用[2]。在恶性肿瘤细胞模型中，3-Bromopyruvic acid作为ATP酶活性抑制剂，可降低ATP水平并通过作用于ATP结合盒转运蛋白拮抗药物外排，从而逆转化疗耐药性[3]。
在体外，25μg/ml 的3-Bromopyruvic acid处理48小时可诱导MCF-7细胞出现典型凋亡形态特征（包括核固缩、胞质颗粒增多），并显著降低Bcl-2、c-Myc和突变型p53表达[4]。40μM的3-Bromopyruvic acid处理2小时能显著降低U118胶质母细胞瘤细胞活力，增加线粒体活性氧（ROS）生成[5]。100μM的3-Bromopyruvic acid处理12小时可诱导THP-1细胞DNA断裂，触发H2A.X磷酸化[6]。
在体内，胰腺癌小鼠模型经腹腔注射3-Bromopyruvic acid（20mg/kg；隔日一次；持续30天）后，肿瘤生长显著抑制、生存期延长，肿瘤组织中髓系抑制细胞数量减少且CD8+ T细胞浸润增加[7]。SW480细胞的异种移植瘤小鼠模型经腹腔注射3-Bromopyruvic acid（8mg/kg；每4天一次；持续28天）可显著抑制肿瘤进展，导致肿瘤组织血管分布紊乱、细胞核固缩及炎性细胞浸润[8]。
| Cell experiment [1]: | |
Cell lines | SW480 cells |
Preparation Method | SW480 cells were cultured in high glucose Dames Modified Eagle's Medium (DMEM) medium. The medium was supplemented with 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. The culture temperature was 37°C and the air concentration was 95%, with a carbon dioxide concentration of 5%. The SW480 cells were seeded at a density of 6×103 cells per well in a 96-well plate and treated with different concentrations of 3-Bromopyruvic acid (0, 40, 80, 160, and 320μM). At 24, 48 and 72 hours, MTT (5mg/ml phosphate-buffered saline, PBS) was added and incubated at 37°C for 4 hours. After 4 hours, the solution was replaced with 150μl dimethyl sulfoxide (DMSO), and 30 minutes later, the absorbance was measured at 490nm using an enzyme reader to determine cell viability. |
Reaction Conditions | 0, 40, 80, 160, and 320μM; 24h |
Applications | 3-Bromopyruvic acid treatment significantly inhibited the cell viability of SW480 cells in dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Panc-2 cells were subcutaneously injected into the right abdomen of 8-week-old female C57BL/6 mice. During anesthesia of the mice, 3.5-4% isoflurane and 100% oxygen were used. For tumor implantation, the uncombined Panc-2 cells were digested with trypsin, washed with cold 1 × PBS, and then mixed 1 × 106 cells with Matrigel at a 1:1 ratio (50µl + 50µl), and injected into a 0.5ml cold syringe equipped with a 27-1/2-gauge needle. The cell mixture (100µl) was carefully injected subcutaneously into the right abdomen of the mice. One week later, the tumor volume (approximately 100mm3) was measured, and the mice were randomly divided into 4 groups (n = 8 mice per group). The mice received vehicle control (only saline and buffer) and 20mg/kg 3-Bromopyruvic acid treatment via intraperitoneal (IP) injection every other day for 30 days. After the treatment period, the mice were euthanized, the tumors were imaged and processed for further analysis. The tumor volume was measured every day using a digital caliper, using the formula: volume = (L×W2)/2, where L = larger length, W = smaller length. The body weight was measured once a week. |
Dosage form | 20mg/kg every other day for 30 days; i.p. |
Applications | 3-Bromopyruvic acid treatment reduced the growth of pancreatic tumors and prolonged the survival period of the mice. |
References: | |
| Cas No. | 1113-59-3 | SDF | |
| 别名 | 3-溴丙酮酸; Bromopyruvic acid; Hexokinase II Inhibitor II, 3-BP | ||
| 化学名 | 3-bromo-2-oxopropanoic acid | ||
| Canonical SMILES | BrCC(C(O)=O)=O | ||
| 分子式 | C3H3BrO3 | 分子量 | 166.96 |
| 溶解度 | ≥ 16.7mg/mL in Water | 储存条件 | Store at 2-8°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.9895 mL | 29.9473 mL | 59.8946 mL |
| 5 mM | 1.1979 mL | 5.9895 mL | 11.9789 mL |
| 10 mM | 0.5989 mL | 2.9947 mL | 5.9895 mL |
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