Alagebrium chloride (ALT711)
(Synonyms: 阿拉氯胺; ALT711) 目录号 : GC33761
Alagebrium chloride (ALT711) (ALT711) 是一种晚期糖基化终产物 (AGE) 抑制剂。
Cas No.:341028-37-3
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
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Cell experiment: |
Human aortic endothelial cells (HAECs) are seeded on decellularized matrices derived from the abdominal aorta (AAo) of Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats with or without Alagebrium (ALT-711) (20 μg/mL in Dulbecco's PBS with 1× antibiotic-antimycotic). Experiments are performed when cells reach 80 to 90% confluence. Flow chambers are sealed to the HAEC monolayers via a vacuum network. Flow is driven by a Masterflex L/S peristaltic pump in a humidified chamber heated to 37°C for 4 h. Leibovitz-15 medium, supplemented with 10% FBS, endothelial BulletKit, and 1× antibiotic-antimycotic solution, is used as the flow medium to maintain pH in the absence of CO2[2]. |
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Animal experiment: |
RAGE apoE mice are randomized to be treated with Alagebrium (1 mg/kg/day by gavage), or no treatment (n=20/group). After 20 weeks of diabetes, mice are placed into individual metabolic cages for 24 h and urine is collected. Body weight as well as fluid and food intake are recorded. Urinary albumin excretion is estimated in urine samples by a mouse albumin enzyme-linked immunosorbent assay (ELISA) kit according to the kit protocol. Urinary and serum creatinine concentrations are measured by high-performance liquid chromatography (HPLC). Systolic blood pressure is assessed by a noninvasive tail cuff method in conscious mice at the end of the study[1]. |
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References: [1]. Watson AM, et al. Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing RAGEactivation in diabetic apolipoprotein E knockout mice. Diabetes. 2012 Aug;61(8):2105-13. |
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Alagebrium chloride is an advanced glycation end product (AGE) inhibitor.
Alagebrium chloride is an advanced glycation end product (AGE) inhibitor. Endothelial cell (EC) proliferation is increased for all groups receiving Alagebrium (ALT-711), particularly when seeded on matrix from the AAo of obese (ZO) and diabetic (ZD) rats[2].
Blood pressure is not affected by treatment with Alagebrium. In diabetic RAGE apoE double-KO mice, treatment with Alagebrium is associated with a modest reduction in renal mass and reduces hyperfiltration compare with nontreated mice. Treatment with Alagebrium in diabetic RAGE apoE double-KO mice is associated with a further reduction in glomerular collagen IV levels, approaching levels observed in control mice[1]. Body weight, heart rate (HR), and mean blood pressure (BP) are similar in Zucker lean (ZL), obese (ZO), and diabetic (ZD) groups in the absence or presence of Alagebrium (ALT-711). Alagebrium increases blood flow (BF) in ZO rats but reduces distal vascular resistance in ZD rats. A decrease in neointimal hyperplasia (NH) intrastrut thickness as a function of local radius is found in all groups with Alagebrium treatment. A significant increase in TGF-β expression is also found in the AAo of ZL rats treated with Alagebrium[2].
[1]. Watson AM, et al. Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing RAGEactivation in diabetic apolipoprotein E knockout mice. Diabetes. 2012 Aug;61(8):2105-13. [2]. Wang H, et al. Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats. Am J Physiol Heart Circ Physiol. 2015 Oct;309(7):H1130-40.
| Cas No. | 341028-37-3 | SDF | |
| 别名 | 阿拉氯胺; ALT711 | ||
| Canonical SMILES | O=C(C1=CC=CC=C1)C[N+]2=CSC(C)=C2C.[Cl-] | ||
| 分子式 | C13H14ClNOS | 分子量 | 267.77 |
| 溶解度 | Water : 50 mg/mL (186.73 mM);DMSO : ≥ 25 mg/mL (93.36 mM) | 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 | 3.7345 mL | 18.6727 mL | 37.3455 mL |
| 5 mM | 0.7469 mL | 3.7345 mL | 7.4691 mL |
| 10 mM | 0.3735 mL | 1.8673 mL | 3.7345 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。
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Alagebrium chloride, a novel advanced glycation end-product cross linkage breaker, inhibits neointimal proliferation in a diabetic rat carotid balloon injury model
Korean Circ J 2010 Oct;40(10):520-6.PMID:21088756DOI:10.4070/kcj.2010.40.10.520.
Background and objectives: Vascular perturbation induced by advanced glycation end-products (AGEs) leads to progression of atherosclerosis, plaque instability, and vascular inflammation, which results in a higher risk of neointimal proliferation. Here we investigated the inhibitory effect of Alagebrium chloride (ALT-711), a breaker of AGE-based cross links, on neointimal proliferation in a carotid artery balloon injury model in diabetic rats induced by streptozotocin (STZ). Materials and methods: Rat aortic vascular smooth muscle cells (RASMCs) were treated with 1-100 µM of alagebrium added 24 hours before the addition of AGEs. This in vivo study was done using 8-week-old male rats that were injected intraperitoneally with 80 mg/kg STZ. Sixteen weeks later, the diabetic rats were treated with 10 mg/kg alagebrium for 4 weeks, after which carotid artery balloon injury was induced. After 4 weeks, the animals were sacrificed for histological analysis. Results: Proliferation of RASMCs was significantly inhibited in alagebrium-treated cells. Alagebrium dose-dependently inhibited AGE-mediated formation of reactive oxygen species (ROS), extracellular signal-regulated kinase phosphorylation, and cyclooxygenase-2 expression. The cellular mechanisms of AGE-induced connective tissue and extracellular matrix expression were decreased in the alagebrium-treated group. This in vivo study shows that expression of AGE receptors and neointima hyperplasia are significantly suppressed in balloon-injured rats treated with alagebrium. Conclusion: Alagebrium treatment in diabetic rats significantly inhibits neointimal hyperplasia after carotid balloon injury due to its inhibition of intracellular ROS synthesis, which results in inhibition of RASMCs proliferation.
Alagebrium chloride protects the heart against oxidative stress in aging rats
J Gerontol A Biol Sci Med Sci 2009 Jun;64(6):629-35.PMID:19299252DOI:10.1093/gerona/glp023.
To investigate the possible effects of Alagebrium chloride (ALT-711) on oxidative stress (OS) process in aging hearts, we examined the role of ALT-711 in cardiac function and OS in the heart of aging rats. Increased mitochondrial DNA (mtDNA) deletion as well as nearly a twofold increase in advanced glycation end products (AGEs) accumulation were observed in aging heart, whereas only about 50% of the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were seen. However, after treatment with ALT-711, preserved cardiac diastolic function accompanied with reduced mtDNA deletion and about 30% of AGEs decrease was observed in aging hearts. In addition, ALT-711 can increase SOD and GSH-PX activities in aging hearts as well as in cultured cardiomyocytes. In conclusion, our study suggests that AGEs accumulation and the abnormalities in the OS in aging hearts can be attenuated by ALT-711, and this might be a novel underlying mechanism for ALT-711 in the treatment of cardiovascular diseases that develop with aging.
Short Duration Alagebrium chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model
Metabolites 2021 Jun 28;11(7):426.PMID:34203471DOI:10.3390/metabo11070426.
Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with Alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, ALT administered prediabetes (day 50-100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1+ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8+ T cell receptor transgenic T cells, reduced blood glucose concentrations and delayed diabetes, suggesting islet effects rather than immune modulation by ALT. Indeed, ALT did not reduce interferon-γ production by leukocytes from ovalbumin-pre-immunised NODShiLt mice and NODscid recipients given diabetogenic ALT treated NOD splenocytes were not protected against T1D. To elucidate β-cell effects, NOD-derived MIN6N8 β-cell major histocompatibility complex (MHC) Class Ia surface antigens were examined using immunopeptidomics. Overall, no major changes in the immunopeptidome were observed during the various treatments with all peptides exhibiting allele specific consensus binding motifs. As expected, longer MHC Class Ia peptides were captured bound to H-2Db than H-2Kb under all conditions. Moreover, more 10-12 mer peptides were isolated from H-2Db after AGE modified bovine serum albumin (AGE-BSA) treatment, compared with bovine serum albumin (BSA) or AGE-BSA+ALT treatment. Proteomics of MIN6N8 cells showed enrichment of processes associated with catabolism, the immune system, cell cycling and presynaptic endocytosis with AGE-BSA compared with BSA treatments. These data show that short-term ALT intervention, given prediabetes, does not arrest experimental T1D but transiently impacts β-cell function.
AGE-breaker ALT711 reverses glycation-mediated cancer cell migration
Soft Matter 2022 Nov 16;18(44):8504-8513.PMID:36325938DOI:10.1039/d2sm00004k.
Diabetes is associated with increased risk of breast cancer and worse prognoses for cancer patients. Hyperglycemia can result in increased glycation, the process wherein crosslinkages are formed between sugars and extracellular matrix (ECM) proteins through the formation of advanced glycation endproducts (AGEs). Although accumulation of AGEs occurs naturally in vivo over time, it is greatly accelerated by the hyperglycemic environment of diabetic patients. AGE accumulation has been linked to stiffening-related diseases such as hypertension, cancer metastasis, and neurodegenerative disorders. In response, several AGE-inhibiting and AGE-breaking drugs have received significant attention for their ability to reduce AGE accumulation. The resulting effects of these drugs on cell behavior is not well understood. In this study, we measured cancer cell migration in glycated collagen with and without the AGE-breaking drug Alagebrium chloride (ALT711) to investigate the drug's ability to disrupt ECM crosslinks and reduce tumor cell spreading, contractility, and migration. The mechanical properties and chemical composition of collagen glycated with increasing concentrations of glucose with and without ALT711 treatment were measured. Increasing glucose concentration resulted in increased AGE accumulation and matrix stiffness as well as increased cancer cell contractility, elongation, and migration. Treatment with ALT711 significantly lowered AGE accumulation within the collagen, decreased collagen stiffness, and reduced cell migration. These findings suggest that while hyperglycemia can increase collagen matrix stiffness, resulting in increased breast cancer cell migration, an AGE-breaker can reverse this phenotype and may be a viable treatment option for reducing cancer cell migration due to glycation.
The effect of Alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure
J Card Fail 2005 Apr;11(3):191-5.PMID:15812746DOI:10.1016/j.cardfail.2004.09.010.
Background: Despite its high prevalence, optimal therapy for diastolic heart failure (DHF) has not been determined. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose crosslinks and may improve ventricular and arterial compliance. Methods and results: A total of 23 patients, mean age 71 years, with stable DHF, ejection fraction (EF) >50%, were enrolled in a 16-week, open-label trial of alagebrium 420 mg per day. Assessments included: peak exercise oxygen consumption, aortic distensibility, and left ventricular EF and mass by magnetic resonance imaging, Doppler diastolic filling, and quality of life by the Minnesota Living with Heart Failure questionnaire. One patient discontinued treatment because of a myocardial infarction after 12 days of treatment, and a second died suddenly after 10 weeks of treatment. Thus 21 patients completed the study. Left ventricular mass was 124 +/- 35 g at baseline and decreased to 119 +/- 34 g at follow up ( P = .036). This was accompanied by a decrease in the ratio of Doppler early diastolic flow velocity to Doppler early diastolic mitral annulus velocity (E') from 10.6 +/- 2.7 to 9.4 +/- 1.9 ( P = .076) and an increase in E' from 7.3 +/- 1.2 to 8.4 +/- 1.7 cm/s ( P = .045). The Minnesota Living with Heart Failure total score improved from 41 +/- 21 to 32 +/- 21 ( P = .01). There were no changes in EF (64 +/- 4% at baseline), blood pressure, peak exercise oxygen consumption, and aortic distensibility. Conclusion: Sixteen weeks of treatment with the glucose crosslink breaker, alagebrium, resulted in a decrease in left ventricular mass and improvements in left ventricular diastolic filling and quality of life in patient with DHF.