Sodium Oxamate
(Synonyms: 草氨酸钠,Sodium oxamate) 目录号 : GC44911
草酸钠作为 PDK1 和 LDHA 抑制剂，IC50 值 (μg/mL) 为 15.60。
Cas No.:565-73-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- Datasheet
| Cell experiment [1]: | |
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Cell lines |
BRCA ovarian cancer cells:A2780 and SKOV3 |
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Preparation Method |
Cell proliferation is evaluated using a Cell Counting Kit-8. SKOV3 cells and A2780 cells are seeded in a 96-well culture plates at a density of 2 105 cells/well and incubated with different concentrations of the drugs for different times(Sodium oxamate). |
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Reaction Conditions |
50 mM Sodium oxamate for 24 h |
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Applications |
Sodium oxamate enhances the suppressive effects of PARP inhibitors on ovarian cancer without BRCA mutations, remarkably promoting the inhibitory effects of PARP inhibitors on wild-type BRCA ovarian cancer cells. |
| Animal experiment [2]: | |
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Animal models |
Four-week-old male BALB/c nude mice of CRC xenograft |
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Preparation Method |
C. tropicalis was given by multipoint intratumoral injection, twice per week for three weeks.Oxaliplatin (10 mg/kg) and Sodium oxamate (500 mg/kg) were administered by intraperitoneal injection, twice per week for three weeks. The length and width of the tumors were measured every three days. |
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Dosage form |
500 mg/kg Sodium oxamate Twice a week for three weeks |
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Applications |
Sodium oxamate reduces the growth of colorectal cancer in CRC mice, by restoring the down-regulated MMR functional proteins and attenuating chemotherapy resistance to oxaliplatin caused by C. tropicalis. |
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References: [1]. Xiang J, Zhou L, He Y, Wu S. LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells. Aging (Albany NY). 2021 Dec 16;13(24):25920-25930. doi: 10.18632/aging.203780. Epub 2021 Dec 16. PMID: 34919531; PMCID: PMC8751605. [2]. Qu J, Sun Z, Peng C, Li D, Yan W, Xu Z, Hou Y, Shen S, Chen P, Wang T. C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int J Biol Sci. 2021 Jul 2;17(11):2756-2769. doi: 10.7150/ijbs.59262. PMID: 34345205; PMCID: PMC8326116. |
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Sodium oxamate as PDK1 and LDHA inhibitor with IC50 values (μg/mL) of 15.60[1]. Sodium oxamate can specifically inhibit LDH-A. Sodium oxamate by down-regulating CDK1/cyclin B1 Pathway induces G2/M cell cycle arrest and promotes apoptotic targets by increasing ROS production in mitochondria[4,5].
Sodium oxamate enhances the suppressive effects of PARP inhibitors on ovarian cancer without BRCA mutations, remarkably promoting the inhibitory effects of PARP inhibitors on wild-type BRCA ovarian cancer cells[3]. In the human PC cell line, Sodium oxamate caused cell inhibition, resulting in increased sensitivity of CRPC cells to DOC, and the combination of DOC and Sodium oxamate promoted apoptosis compared with DOC or Sodium oxamate alone[2].
Sodium oxamate reduces the growth of colorectal cancer in CRC mice, by restoring the down-regulated MMR functional proteins and attenuating chemotherapy resistance to oxaliplatin caused by C. tropicalis[6]. NETosis and lactate accumulation during LPS induced sepsis in mice was inhibited by sodium oxamate [7].
References:
[1]: Kamal S, Derbala HA, et,al. Synthesis, Biological, and Molecular Docking Studies on 4,5,6,7-Tetrahydrobenzo[b]thiophene Derivatives and Their Nanoparticles Targeting Colorectal Cancer. ACS Omega. 2021 Oct 25;6(43):28992-29008. doi: 10.1021/acsomega.1c04063. PMID: 34746589; PMCID: PMC8567357.
[2]: Muramatsu H, Sumitomo M, et,al. Targeting lactate dehydrogenase?A promotes docetaxel?induced cytotoxicity predominantly in castration?resistant prostate cancer cells. Oncol Rep. 2019 Jul;42(1):224-230. doi: 10.3892/or.2019.7171. Epub 2019 May 24. PMID: 31180564.
[3]: Xiang J, Zhou L, et,al. LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells. Aging (Albany NY). 2021 Dec 16;13(24):25920-25930. doi: 10.18632/aging.203780. Epub 2021 Dec 16. PMID: 34919531; PMCID: PMC8751605.
[4]: Thornburg JM, Nelson KK, et,al. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res. 2008;10(5):R84. doi: 10.1186/bcr2154. Epub 2008 Oct 15. PMID: 18922152; PMCID: PMC2614520.
[5]: Zhai X, Yang Y, et,al. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep. 2013 Dec;30(6):2983-91. doi: 10.3892/or.2013.2735. Epub 2013 Sep 19. PMID: 24064966.
[6]: Qu J, Sun Z, et,al. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int J Biol Sci. 2021 Jul 2;17(11):2756-2769. doi: 10.7150/ijbs.59262. PMID: 34345205; PMCID: PMC8326116.
[7]: Awasthi D, Nagarkoti S, et,al. Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis. Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165542. doi: 10.1016/j.bbadis.2019.165542. Epub 2019 Aug 29. PMID: 31473341.
草酸钠作为 PDK1 和 LDHA 抑制剂,IC50 值 (μg/mL) 为 15.60[1]。草酸钠可以特异性抑制LDH-A。草酸钠通过下调 CDK1/cyclin B1 通路诱导 G2/M 细胞周期停滞,并通过增加线粒体中 ROS 的产生促进凋亡靶点[4,5]。
草酸钠增强PARP抑制剂对无BRCA突变卵巢癌的抑制作用,显着促进PARP抑制剂对野生型BRCA卵巢癌细胞的抑制作用[3]。在人 PC 细胞系中,草酸钠引起细胞抑制,导致 CRPC 细胞对 DOC 的敏感性增加,与单独使用 DOC 或草酸钠相比,DOC 和草酸钠联合促进细胞凋亡[2] .
草酸钠通过恢复下调的 MMR 功能蛋白和减弱由热带念珠菌引起的对奥沙利铂的化疗耐药性来减少 CRC 小鼠结直肠癌的生长[6]。草胺酸钠可抑制 LPS 诱导小鼠脓毒症期间的 NETosis 和乳酸积累[7]。
| Cas No. | 565-73-1 | SDF | |
| 别名 | 草氨酸钠,Sodium oxamate | ||
| Canonical SMILES | [O-]C(C(N)=O)=O.[Na+] | ||
| 分子式 | C2H2NO3•Na | 分子量 | 111 |
| 溶解度 | ≥ 11.1mg/mL in Water | 储存条件 | Store at -20°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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 9.009 mL | 45.045 mL | 90.0901 mL |
| 5 mM | 1.8018 mL | 9.009 mL | 18.018 mL |
| 10 mM | 0.9009 mL | 4.5045 mL | 9.009 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sodium Oxamate reduces lactate production to improve the glucose homeostasis of Micropterus salmoides fed high-carbohydrate diets
Am J Physiol Regul Integr Comp Physiol 2023 Feb 1;324(2):R227-R241.PMID:36572554DOI:10.1152/ajpregu.00226.2022.
The study was performed to evaluate the effects of the reduced lactate production by Sodium Oxamate (SO) on growth performance, lactate and glucose and lipid metabolism, and glucose tolerance of Micropterus salmoides fed high-carbohydrate (CHO) diets. In in vitro study, primary hepatocytes were incubated for 48 h in a control medium (5.5 mM glucose), a high-glucose medium (25 mM glucose, HG), or a SO-containing high-glucose medium (25 mM glucose + 50 mM SO, HG-SO). Results indicated lactate and triglyceride (TG) levels, and lactate dehydrogenase a (LDH-a) expression in the HG-SO group were remarkably lower than those of the HG group. In in vivo study, M. salmoides (5.23 ± 0.03 g) were fed four diets containing a control diet (10% CHO, C) and three SO contents [0 (HC), 100 (HC-SO1), and 200 (HC-SO2) mg·kg-1, respectively] of high-CHO diets (20% CHO) for 11 wk. High-CHO diets significantly reduced weight gain rate (WGR), specific growth rate (SGR), p-AMPK-to-t-AMPK ratio, and expression of insulin receptor substrate 1 (IRS1), insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), fructose-1,6-biphosphatase (FBPase), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase 1α (CPT1α) compared with the C group, whereas the opposite was true for plasma levels of glucose, TG, lactate, tissue glycogen, and lipid contents, and expression of LDH-a, monocarboxylate transporter 1 and 4 (MCT1 and MCT4), insulin, glucokinase (GK), pyruvate dehydrogenase E1 subunit (PDH), sterol-regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). The HC-SO2 diets remarkably increased WGR, SGR, p-AMPK-to-t-AMPK ratio, and expression of IRS1, IGF-I, IGF-IR, GK, PDHα, PDHβ, FAS, acetyl-CoA carboxylase 1 (ACC1), PPARα, and CPT1α compared with the HC group. Besides, HC-SO2 diets also enhanced glucose tolerance of fish after a glucose loading. Overall, the reduced lactate production by SO benefits growth performance and glucose homeostasis of high-CHO-fed M. salmoides through the enhancement of glycolysis, lipogenesis, and fatty acid β-oxidation coupled with the suppression of glycogenesis and gluconeogenesis.
Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1α
Front Oncol 2021 May 26;11:594200.PMID:34123772DOI:10.3389/fonc.2021.594200.
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide in both sexes. Current therapies include surgery, chemotherapy, and targeted therapy; however, prolonged exposure to chemical agents induces toxicity in patients and drug resistance. So, we implemented a therapeutic strategy based on the combination of doxorubicin, metformin, and Sodium Oxamate called triple therapy (Tt). We found that Tt significantly reduced proliferation by inhibiting the mTOR/AKT pathway and promoted apoptosis and autophagy in CRC derived cells compared with doxorubicin. Several autophagy genes were assessed by western blot; ULK1, ATG4, and LC3 II were overexpressed by Tt. Interestingly, ULK1 was the only one autophagy-related protein gradually overexpressed during Tt administration. Thus, we assumed that there was a post-transcriptional mechanism mediating by microRNAs that regulate UKL1 expression during autophagy activation. Through bioinformatics approaches, we ascertained that ULK1 could be targeted by mir-26a, which is overexpressed in advanced stages of CRC. In vitro experiments revealed that overexpression of mir-26a decreased significantly ULK1, mRNA, and protein expression. Contrariwise, the Tt recovered ULK1 expression by mir-26a decrease. Due to triple therapy repressed mir-26a expression, we hypothesized this drug combination could be involved in mir-26a transcription regulation. Consequently, we analyzed the mir-26a promoter sequence and found two HIF-1α transcription factor recognition sites. We developed two different HIF-1α stabilization models. Both showed mir-26a overexpression and ULK1 reduction in hypoxic conditions. Immunoprecipitation experiments were performed and HIF-1α enrichment was observed in mir-26a promoter. Surprisingly, Tt diminished HIF-1α detection and restored ULK1 mRNA expression. These results reveal an important regulation mechanism controlled by the signaling that activates HIF-1α and that in turn regulates mir-26a transcription.
Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans
Front Physiol 2022 Aug 30;13:951390.PMID:36111162DOI:10.3389/fphys.2022.951390.
Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.1 ± 0.5 kg/m2) and fourteen obese (40.6 ± 1.4 kg/m2) adults underwent a muscle biopsy and 2-h oral glucose tolerance test. Skeletal muscle lactylation was increased in obese compared to lean females (19%, p < 0.05) and associated with insulin resistance (r = 0.37, p < 0.05) in the whole group. Skeletal muscle lactylation levels were significantly associated with markers of anaerobic metabolism (plasma lactate and skeletal muscle lactate dehydrogenase [LDH], p < 0.05) and negatively associated with markers of oxidative metabolism (skeletal muscle cytochrome c oxidase subunit 4 and Complex I [pyruvate] OXPHOS capacity, p < 0.05). Treatment of primary human skeletal muscle cells (HSkMC) with sodium lactate for 24 h increased protein lactylation and IRS-1 serine 636 phosphorylation in a similar dose-dependent manner (p < 0.05). Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with Sodium Oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.
Oxamate, an inhibitor of lactate dehydrogenase, can stimulate M2 polarization of peritoneal macrophages in mice with Lewis lung carcinoma
Exp Oncol 2021 Sep;43(3):270-273.PMID:34591427DOI:10.32471/exp-oncology.2312-8852.vol-43-no-3.16530.
Background: Inhibition of aerobic glycolysis of cancer cells is considered a promising therapeutic strategy for the treatment of neoplasms. Some inhibitors of energy metabolism can affect not only tumor cells but also the functional polarization of tumor-associated macrophages, which may either enhance the antitumor effect of such agents or impair their antitumor efficacy. Aim: To investigate the effect of oxamate, a lactate dehydrogenase (LDH) inhibitor, on the polarization of peritoneal macrophages (PMP) in both intact mice and mice with transplanted Lewis lung carcinoma (LLC). Materials and methods: The low-metastatic LLC variant, LLC/R9, was transplanted to female C57Bl/6 mice. Sodium Oxamate was used as the test agent at concentrations of 0.02, 0.2, and 2 mg/ml. Macrophage polarization in tumor-bearing mice was estimated on day 23 after tumor transplantation by assessing nitric oxide (NO) production and arginase activity as functional indices of PMPs polarization. Results: Oxamate can affect the functional polarization of PMPs in both intact mice and animals with transplanted LLC/R9. Oxamate in all studied concentrations changed the markers of PMPs polarization in intact mice (decreasing NO levels and activating arginase activity) that indicated the stimulation of M2 polarization. In tumor-bearing animals, stimulation of M2 polarization is observed at low concentrations of oxamate (0.02 mg/ml), but its high concentrations (2.0 mg/ml) causes M1 polarization, which is characterized by three-fold increase in the level of NO and a decrease in the level of arginase activity. Conclusion: Oxamate, an inhibitor of LDH, can stimulate M2 polarization of peritoneal macrophages of mice bearing LLC in a dose-dependent manner.
Siah2 inhibitor and the metabolic antagonist Oxamate retard colon cancer progression and downregulate PD1 expression
Recent Pat Anticancer Drug Discov 2023 Jan 16.PMID:36650629DOI:10.2174/1574892818666230116142606.
Background: Solid tumors such as colon cancer are characterized by rapid and sustained cell proliferation, which ultimately results in hypoxia, induction of hypoxia-inducible factor-1α (HIF-1α), and activation of glycolysis to promote tumor survival and immune evasion. We hypothesized that a combinatorial approach of menadione (MEN) as an indirect HIF-1α inhibitor and Sodium Oxamate (OX) as a glycolysis inhibitor may be a promising treatment strategy for colon cancer. Objectives: We investigated the potential efficacy of this combination for promoting an antitumor immune response and suppressing tumor growth in a rat model of colon cancer. Methods: Colon cancer was induced by once-weekly subcutaneous injection of 20 mg/kg dimethylhydrazine (DMH) for 16 weeks. Control rats received the vehicle and then no further treatment (negative control) or MEN plus OX for 4 weeks (drug control). Dimethylhydrazine-treated rats were then randomly allocated to four groups: DMH alone group and other groups treated with MEN, OX, and a combination of (MEN and OX) for 4 weeks. Serum samples were assayed for the tumor marker carbohydrate antigen (CA19.9), while expression levels of HIF-1α, caspase-3, PHD3, LDH, and PD1 were evaluated in colon tissue samples by immunoassay and qRT-PCR. Additionally, Ki-67 and Siah2 expression levels were examined by immunohistochemistry. Results: The combination of MEN plus OX demonstrated a greater inhibitory effect on the expression levels of HIF-1α, Siah2, LDH, Ki-67, and PD1, and greater enhancement of caspase-3 and PHD3 expression in colon cancer tissues than either drug alone. Conclusion: Simultaneous targeting of hypoxia and glycolysis pathways by a combination of MEN and OX could be a promising therapy for inhibiting colon cancer cell growth and promoting antitumor immunity [1].