AICAR
(Synonyms: 阿卡地新; Acadesine; AICA Riboside) 目录号 : GC10518
An activator of AMPK
Cas No.:2627-69-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Nine human MCL cell lines (GRANTA-519, JVM-2, JEKO-1, Z-138, MAVER-1, REC-1, UPN-1, HBL-2 and MINO) |
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Preparation Method |
MCL cell lines were incubated with AICAR at doses ranging from 0.1 to 2 mM for 24 or 48 hours. |
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Reaction Conditions |
0.1 to 2 mM for 24 or 48 hours. |
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Applications |
Most of the cell lines analyzed (REC-1, JEKO-1, UPN-1, JVM-2, MAVER-1 and Z-138) showed a IC50 lower than 1 mM after 48 hours of acadesine incubation. |
| Animal experiment [2]: | |
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Animal models |
Female Nude NMRI Mice |
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Preparation Method |
Mice were randomized into two experimental groups, each containing 15 animals. Animals in both groups received a 100 µl injection of 5*106 K562 leukemia cells on both flanks. When tumors reached 150-200 mm3, animals were injected intraperitoneally with NaCl 0.9% or AICAR at dose level of 50 mg/kg body weight. |
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Dosage form |
Intraperitoneal injection, 0, 0.25, 0.5, 1 or 2 mg |
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Applications |
AICAR significantly reduced tumor formation in nude mice. Statistical analysis of tumor size shows a robust reduction of 68% at day 16 and 51% at day 20. |
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References: [1]: Montraveta A, Xargay-Torrent S, LÓpez-Guerra M, et al. Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma[J]. Oncotarget, 2014, 5(3): 726. |
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AICAR (also called acadesine) is a purine nucleoside. Three pharmacological applications of AICAR were identified: i) stimulation under ischemic conditions of the cardiac production of the vasodilator, adenosine [1]; ii) inhibition of hepatic gluconeogenesis at the level of fructose-1,6-bisphosphatase [2], of therapeutic potential in diabetes; and iii) stimulation of AMP-activated protein kinase (AMPK), initially applied to inhibit the hepatic synthesis of triglycerides and cholesterol [3].
AICAR (treated 48 hours) inhibited cell proliferation of mantle cell lymphoma (MCL) cell lines, REC-1, JEKO-1, UPN-1, JVM-2, MAVER-1 and Z-138, with IC50s of 0.28, 0.59, 0.64, 0.98, 0.50, and 0.14 Mm respectively [4]. AICAR inhibited the growth and depletion of pyrimidine nucleotide pools in fibroblasts [5], accelerated repletion of purine nucleotide pools in heart [6], inhibition of fatty acid, sterol synthesis, and gluconeogenesis in hepatocytes, and increase in glucose uptake in muscle [7].
AICAR (500 mg/kg) injected intraperitoneally into C57BL/6J mice 1 hour before LPS administration. LPS induced the expression of TF mRNA in many major organs, including the lung and liver [8]. A daily administration of 400mg/kg AICAR in mice previously inoculated with a MCL xenotransplant significantly reduced tumor burden when compared to control animals, as soon as 7 days of treatment [9].
References:
[1]. Gruber H E, Hoffer M E, McAllister D R, et al. Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury[J]. Circulation, 1989, 80(5): 1400-1411.
[2]. Vincent M F, Marangos P J, Gruber H E, et al. Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes[J]. Diabetes, 1991, 40(10): 1259-1266.
[3]. Hardie D G, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell?[J]. Annual review of biochemistry, 1998, 67: 821.
[4]. Montraveta A, Xargay-Torrent S, López-Guerra M, et al. Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma[J]. Oncotarget, 2014, 5(3): 726.
[5]. Sabina R L, Patterson D, Holmes E W. 5-Amino-4-imidazolecarboxamide riboside (Z-riboside) metabolism in eukaryotic cells[J]. Journal of Biological Chemistry, 1985, 260(10): 6107-6114.
[6]. Swain J L, Hines J J, Sabina R L, et al. Accelerated repletion of ATP and GTP pools in postischemic canine myocardium using a precursor of purine de novo synthesis[J]. Circulation Research, 1982, 51(1): 102-105.
[7]. Hardie D G, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell?[J]. Annual review of biochemistry, 1998, 67: 821.
[8]. Zhang W, Wang J, Wang H, et al. Acadesine inhibits tissue factor induction and thrombus formation by activating the phosphoinositide 3-kinase/Akt signaling pathway[J]. Arteriosclerosis, thrombosis, and vascular biology, 2010, 30(5): 1000-1006.
[9]. Montraveta A, de Fri?as M, Campa?s C, et al. The Nucleoside Analogue Acadesine Exerts Antitumoral Activity and Cooperates with Conventional Agents In In Vitro and In Vivo Models of Mantle Cell Lymphoma[J]. Blood, 2010, 116(21): 3918.
AICAR（也称为 acadesine）是一种嘌呤核苷。确定了 AICAR 的三种药理学应用:i) 在缺血条件下刺激心脏产生血管扩张剂腺苷 [1]； ii) 在 fructose-1,6-bisphosphatase [2] 水平抑制肝糖异生，具有治疗糖尿病的潜力； iii) 刺激 AMP 活化蛋白激酶 (AMPK)，最初用于抑制肝脏合成甘油三酯和胆固醇[3]。
AICAR（处理 48 小时）抑制套细胞淋巴瘤 (MCL) 细胞系 REC-1、JEKO-1、UPN-1、JVM-2、MAVER-1 和 Z-138 的细胞增殖，IC50 为 0.28 , 0.59, 0.64, 0.98, 0.50, 0.14 Mm [4]。 AICAR 抑制成纤维细胞 [5] 中嘧啶核苷酸库的生长和消耗，加速心脏中嘌呤核苷酸库的补充 [6]，抑制脂肪酸、甾醇合成，和肝细胞中的糖异生，以及肌肉中葡萄糖摄取的增加[7]。
AICAR (500 mg/kg) 在 LPS 给药前 1 小时腹膜内注射到 C57BL/6J 小鼠中。 LPS 在许多主要器官中诱导 TF mRNA 的表达，包括肺和肝[8]。与对照动物相比，在预先接种 MCL 异种移植物的小鼠中每天给予 400 毫克/千克 AICAR，只要治疗 7 天[9]。
| Cas No. | 2627-69-2 | SDF | |
| 别名 | 阿卡地新; Acadesine; AICA Riboside | ||
| 化学名 | 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]imidazole-4-carboxamide | ||
| Canonical SMILES | CC(C=C(C)C=CC(=O)NO)C(=O)C1=CC=C(C=C1)N(C)C | ||
| 分子式 | C9H14N4O5 | 分子量 | 258.23 |
| 溶解度 | ≥ 12.9 mg/mL in DMSO, ≥ 52.9 mg/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 | 3.8725 mL | 19.3626 mL | 38.7252 mL |
| 5 mM | 0.7745 mL | 3.8725 mL | 7.745 mL |
| 10 mM | 0.3873 mL | 1.9363 mL | 3.8725 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。
AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies on the role of AMPK, both in the physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK-activator. Even with more complex models of AMPK downregulation and knockout being introduced, AICAr remained a regular starting point for many studies focusing on AMPK biology. However, there is an increasing number of studies showing that numerous AICAr effects, previously attributed to AMPK activation, are in fact AMPK-independent. This review aims to give an overview of the present knowledge on AMPK-dependent and AMPK-independent effects of AICAr on metabolism, hypoxia, exercise, nucleotide synthesis, and cancer, calling for caution in the interpretation of AICAr-based studies in the context of understanding AMPK signaling pathway.
AICAR stimulates mitochondrial biogenesis and BCAA catabolic enzyme expression in C2C12 myotubes
Type 2 diabetes is characterized by reduced insulin sensitivity, elevated blood metabolites, and reduced mitochondrial metabolism. Insulin resistant populations often exhibit reduced expression of genes governing mitochondrial metabolism such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Interestingly, PGC-1α regulates the expression of branched-chain amino acid (BCAA) metabolism, and thus, the consistently observed increased circulating levels of BCAA in diabetics may be partially explained by reduced PGC-1α expression. Conversely, PGC-1α upregulation appears to increase BCAA catabolism. PGC-1α activity is regulated by 5'-AMP-activated protein kinase (AMPK), however, only limited experimental data exists on the effect of AMPK activation in the regulation of BCAA catabolism. The present report examined the effects of the commonly used AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on the metabolism and expression of several related targets (including BCAA catabolic enzymes) of cultured myotubes. C2C12 myotubes were treated with AICAR at 1 mM for up to 24 h. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Metabolic gene and protein expression were assessed via qRT-PCR and western blot, respectively. AICAR treatment significantly increased mitochondrial content and peak mitochondrial capacity. AICAR treatment also increased AMPK activation and mRNA expression of several regulators of mitochondrial biogenesis but reduced glycolytic metabolism and mRNA expression of several glycolytic enzymes. Interestingly, branched-chain alpha-keto acid dehydrogenase a (BCKDHa) protein was significantly increased following AICAR-treatment suggesting increased overall BCAA catabolic capacity in AICAR-treated cells. Together, these experiments demonstrate AICAR/AMPK activation can upregulate BCAA catabolic machinery in a model of skeletal muscle.
AICAR attenuates postoperative abdominal adhesion formation by inhibiting oxidative stress and promoting mesothelial cell repair
Background: Postoperative abdominal adhesion is one of most common complications after abdominal operations. 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) is an adenosine 5'-monophosphate activated protein kinase (AMPK) pathway agonist that inhibits inflammation, reduces cell fibrosis and cellular reactive oxygen species (ROS) injury, promotes autophagy and mitochondrial function. This study aimed to explore the mechanism of AICAR in inhibiting adhesion formation.
Materials and methods: Forty rats were randomly divided into five groups. All of the rats except the sham group received cecal abrasion to establish an adhesion model. The rats in the sodium hyaluronate group were treated with 2 mL sodium hyaluronate before closing the peritoneal cavity. The AICAR 1 and 2 groups were treated with 100 mg/kg and 200 mg/kg AICAR, respectively. Seven days after the operation, all of the rats were euthanized, and the adhesion condition was evaluated by Nair's system. Inflammation was assessed by Eosin-hematoxylin (HE) staining and transforming growth factor-β (TGF-β1) detection. Oxidative stress effect was determined by ROS, nitric oxide (NO) level, superoxide dismutase (SOD), catalase, glutathione peroxidase (Gpx) and malondialdehyde (MDA) levels in adhesion tissue. Then, Sirius red picric acid staining was used to detect the fiber thickness. Immunohistochemical staining of cytokeratin-19 (CK-19), alpha-smooth muscle actin (α-SMA) and nuclear factor erythroid 2-related factor 2 (Nrf2) was also performed. Finally, HMrSV5 cells were treated with TGF-β1 and AICAR, the mRNA expression of E-cadherin, α-SMA and vimentin was assessed by q-PCR and cellular immunofluorescent staining.
Results: The rats in the AICAR-treated group had fewer adhesion formation incidences and a reduced Nair's score. The inflammation was determined by HE staining and TGF-β1 concentration. The ROS, SOD, Catalase, Gpx, MDA levels and fiber thickness were decreased by AICAR treatments compared to the control. However, the NO production, Nrf2 levels and peritoneal mesothelial cell integrity were promoted after AICAR treatments. In vitro work, AICAR treatments reduced E-cadherin, α-SMA and vimentin mRNA level compared to that in the TGF-β1 group.
Conclusion: AICAR can inhibit postoperative adhesion formation by reducing inflammation, decreasing oxidative stress response and promoting peritoneal mesothelial cell repair.
Aicar effect in early neuronal development
The neurological manifestations of Lesch-Nyhan disease (LND) have been attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on nervous system development. An increase has been reported in the levels of 5-aminoimidazole-4-carboxamide-1-β-D-ribotide (AICAR) and its triphosphate form ZTP in the red blood cells of patients with LND. AICAR accumulation in the brain has been hypothesized as the cause of some of the neurological symptoms of patients with LND. In this study, we examined the effect of AICAR on the differentiation of neurons in the well-established human NTERA-2 cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model. NT2/D1 cells were differentiated along neuroectodermal lineages after exposure to 10-?M retinoic acid (RA), with or without the addition of 25-?M AICAR to the culture medium. The effect of AICAR on RA differentiation were examined through changes in the expression of genes essential to neuronal differentiation, as well as genes from the Wnt/β-catenin, transforming growth factor beta (TGFβ) and sonic hedgehog (SHH) pathways. Results: RA-induced differentiation in the NT2/D1 cells significantly increased the expression of MAP2, NRG1, NRP1, NRP2, NEUROG1 and EN1 genes (genes linked to neural differentiation) compared with undifferentiated NT2/D1 cells. We found that AICAR increased the expression of the SHH gene and the WNT2 and WNT7B genes but did not influence the expression of genes whose overexpression characterize early neurodevelopmental processes. Conclusion: The relevance of the AICAR related changes in the SHH and Wnt/β-catenin pathway genes expression in the physiopathology of LND warrants further exploration.
AICAR Improves Outcomes of Metabolic Syndrome and Type 2 Diabetes Induced by High-Fat Diet in C57Bl/6 Male Mice
The aim of the study was to investigate the effect of AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on the consequences of metabolic syndrome and type 2 diabetes induced by the consumption of a high-fat diet (HFD) in male C57Bl/6 mice. Additionally, the animals from group 6 were administered Methotrexate (MTX) at a dose of 1 mg/kg in parallel with AICAR, which slows down the metabolism of AICAR. The animals were recorded with signs of metabolic syndrome and type 2 diabetes mellitus by recording their body weights, glucose and insulin levels, and the calculating HOMA-IRs. At the end of the study, at the end of the 13th week, during necropsy, the internal organs were assessed, the masses of the organs were recorded, and special attention was paid to visceral fat, assessing its amount and the mass of the fat surrounding epididymis. The biochemical parameters and histology of the internal organs and tissues were assessed. The animals showed signs of metabolic syndrome and type 2 diabetes, namely, weight gain, hyperglycemia, hyperinsulinemia, an increase in the amount and mass of abdominal fat, and metabolic disorders, all expressed in a pathological change in biochemical parameters and pathological changes in internal organs. The AICAR treatment led to a decrease in body weight, a decrease in the amount and mass of abdominal fat, and an improvement in the pathomorphological picture of internal organs. However, some hepatotoxic effects were observed when the animals, on a received standard diet (STD), were treated with AICAR starting from the first day of the study. The additional administration of MTX, an AICAR metabolic inhibitor, did not improve its efficacy. Thus, AICAR has therapeutic potential for the treatment of metabolic syndrome and type 2 diabetes.