LR-90
(Synonyms: 2,2'-((((((亚甲基双(2-氯-4,1-亚苯基))二(氮烷二基))二(羰基))双(氮烷二) 目录号 : GC31437
LR-90是晚期糖基化终产物(advancedglycationendproduct(AGE))抑制剂，能够抑制人单核细胞的炎症反应。LR-90也可用于糖尿病动物模型研究。
Cas No.:245075-84-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LR-90 is an advanced glycation end product (AGE) inhibitor, inhibits inflammatory responses in human monocytes[1]. LR-90 is also used in the research of diabetic animal model[2].
LR-90 (0, 25, 50, 100, and 200 μM) inhibits RAGE, MCP-1, COX-2, IP-10 and NOX2 mRNA expression in THP-1 cells in a dose-dependent manner, after pretreatment 1 h befor S100b stimulatation for 4 hours[1].LR-90 (0, 25, 50, 100, and 200 μM) dose-dependently and significantly blocks THP-1 cells adherence to endothelial cells after pretreatment 1 h befor S100b stimulatation for 24 hours[1].LR-90 (0, 25, 50, 100, and 200 μM, for 24 hours) shows no effect on the cell viability of THP-1 cells[1].|| Cell Viability Assay[1]||Cell Line:|THP-1 cells|Concentration:|0, 25, 50, 100, and 200 μM|Incubation Time:|24 hours|Result:|Showed no cytotoxicity to THP-1 cells.|| RT-PCR[1]||Cell Line:|THP-1 cells|Concentration:|0, 25, 50, 100, and 200 μM|Incubation Time:|One hour before S100b addition for 4 hours|Result:|Dose-dependently inhibited mRNA expression of RAGE, MCP-1, COX-2, IP-10, and NOX2 stimulated with S100b.
LR-90 (50 mg/L, p.o. for 27 weeks) significantly reduces plasma lipids, modestly affects hyperglycaemia in ZDF rats[2].LR-90 (50 mg/L) decreases renal AGE, AGER and lipid peroxidation[2].|| Animal Model:|Male ZDF rats (13 to 40 weeks)[2]|Dosage:|50 mg/L|Administration:|P.O. for 27 weeks|Result:|Significantly reduced plasma triacylglycerol and cholesterol by ∼55% and ∼30%, respectively. Modestly affected hyperglycaemia and blood pressure. Lowered the body weight.
[1]. Figarola JL, et al. Anti-inflammatory effects of the advanced glycation end product inhibitor LR-90 in human monocytes. Diabetes. 2007 Mar;56(3):647-55. [2]. Figarola JL, et al. LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat. Diabetologia. 2008 May;51(5):882-91.
| Cas No. | 245075-84-7 | SDF | |
| 别名 | 2,2'-((((((亚甲基双(2-氯-4,1-亚苯基))二(氮烷二基))二(羰基))双(氮烷二 | ||
| Canonical SMILES | O=C(NC1=CC=C(C=C1)OC(C)(C)C(O)=O)NC(C(Cl)=C2)=CC=C2CC3=CC=C(C(Cl)=C3)NC(NC4=CC=C(C=C4)OC(C)(C)C(O)=O)=O | ||
| 分子式 | C35H34Cl2N4O8 | 分子量 | 709.57 |
| 溶解度 | DMSO : ≥ 100 mg/mL (140.93 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 1.4093 mL | 7.0465 mL | 14.093 mL |
| 5 mM | 0.2819 mL | 1.4093 mL | 2.8186 mL |
| 10 mM | 0.1409 mL | 0.7047 mL | 1.4093 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。
LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells
Methylglyoxal (MGO) is a highly reactive dicarbonyl compound known to induce cellular injury and cytoxicity, including apoptosis in vascular cells. Vascular endothelial cell apoptosis has been implicated in the pathophysiology and progression of atherosclerosis. We investigated whether the advanced glycation end-product inhibitor LR-90 could prevent MGO-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). HUVECs were pre-treated with LR-90 and then stimulated with MGO. Cell morphology, cytotoxicity and apoptosis were evaluated by light microscopy, MTT assay, and Annexin V-FITC and propidium iodide double staining, respectively. Levels of Bax, Bcl-2, cytochrome c, mitogen-activated protein kinases (MAPKs) and caspase activities were assessed by Western blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. LR-90 dose-dependently prevented MGO-associated HUVEC cytotoxicity and apoptotic biochemical changes such as loss of MMP, increased Bax/Bcl-2 protein ratio, mitochondrial cytochrome c release and activation of caspase-3 and 9. Additionally, LR-90 blocked intracellular ROS formation and MAPK (p44/p42, p38, JNK) activation, though the latter seem to be not directly involved in MGO-induced HUVEC apoptosis. LR-90 prevents MGO-induced HUVEC apoptosis by inhibiting ROS and associated mitochondrial-dependent apoptotic signaling cascades, suggesting that LR-90 possess cytoprotective ability which could be beneficial in prevention of diabetic related-atherosclerosis.
LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat
Aims/hypothesis: Previous studies have shown that LR-90, a new inhibitor of AGE formation, prevented the development of experimental type 1 diabetic nephropathy. In this study, we examined the effects of LR-90 in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes and metabolic syndrome, and investigated the mechanisms by which it may protect against renal injury.
Methods: Male ZDF rats were treated without or with LR-90 from age 13 to 40 weeks. Metabolic and kidney functions and renal histology were evaluated. AGE accumulation and the production of the receptor for AGE (AGER) were measured. Profibrotic growth factors, extracellular matrix proteins and intracellular signalling pathways associated with glomerular and tubular damage were also analysed.
Results: LR-90 dramatically reduced plasma lipids in ZDF rats, with only modest effects on hyperglycaemia. Renal AGE, AGER and lipid peroxidation were all attenuated by LR-90. LR-90 significantly retarded the increase in albuminuria and proteinuria. This was associated with reduction in glomerulosclerosis and tubulointerstitial fibrosis, concomitant with marked inhibition of renal overproduction of TGF-beta1, connective tissue growth factor, fibronectin and collagen IV. Additionally, LR-90 downregulated the activation of key mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) in the renal cortex.
Conclusions/interpretation: These results support our earlier studies on the renoprotective effects of LR-90 on type 1 diabetic nephropathy and provide further evidence that LR-90, an AGE inhibitor with pleiotrophic effects, may also be beneficial for the prevention of type 2 diabetic nephropathy, where multiple risk factors, such as hyperglycaemia, dyslipidaemia, obesity, insulin resistance and hypertension, contribute to renal injury.
LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats
Aims/hypothesis: Advanced glycation and lipoxidation endproducts have been implicated in the pathogenesis of diabetic complications, including diabetic nephropathy. LR-90, a new advanced glycation endproduct inhibitor, was investigated for its effects on the development of renal disease in diabetic rats.
Methods: Diabetic animals were randomly allocated into groups receiving LR-90 or vehicle (untreated). Age- and weight-matched non-diabetic rats were studied concurrently. Body weight, plasma glucose, glycated haemoglobin, urinary albumin and creatine excretions were measured serially. Kidney histopathology, AGE accumulation in cells and tissues, protein oxidation, were also examined. In vitro assays were used to assess the possible mechanism of action of LR-90.
Results: LR-90 inhibited the increase in albumin and creatinine concentrations, and concentrations of circulating AGE in diabetic rats without any effect on glycaemic control. LR-90 treated-rats also showed higher body weights than untreated diabetic rats. LR-90 prevented glomerulosclerosis, tubular degeneration and collagen deposition in the kidney. AGE-induced cross-linking and fluorescence of tail collagen were reduced by LR-90 treatment. LR-90 also decreased AGE accumulation in kidney glomeruli and nitrotyrosine deposition in the renal cortex. In vitro, LR-90 was capable of reacting with reactive carbonyl compounds and was a more potent metal chelator than pyridoxamine and aminoguanidine.
Conclusion/interpretation: LR-90 reduces in vivo AGE accumulation, AGE-protein cross-linking and protein oxidation, and could be beneficial in preventing the progression of diabetic nephropathy. The AGE inhibitory and therapeutic effects of LR-90 could be attributed, at least in part, to its ability to react with reactive carbonyl species and/or potent metal chelating activity that inhibits glycoxidative-AGE formation.
A new advanced glycation inhibitor, LR-90, prevents experimental diabetic retinopathy in rats
Background: Diabetic retinopathy is associated with accumulation of advanced glycation end products in the retinal microvasculature. LR-90 is an effective multistage inhibitor of advanced glycation with renoprotective and anti-inflammatory properties.
Aim: To explore the role of LR-90 in the progression of experimental diabetic retinopathy.
Methods: Streptozotocin-induced diabetic Sprague-Dawley rats were treated with LR-90 (50 mg/l in drinking water) for up to 32 weeks. At the end of the study, eyes were enucleated and subjected to trypsin digestion and staining with light green/haematoxylin. Acellular capillaries and pericytes were quantified in random fields using light microscopy.
Results: In the LR-90-treated diabetic animals, acellular capillary numbers were reduced to 1.63 (0.20) from 2.58 (0.49) (p<0.05) in diabetic controls. LR-90 treatment also restored the pericyte deficit from 18.12 (0.98) in diabetic rats to 24.19 (0.76) (p<0.001).
Conclusion: These findings show that LR-90 can effectively inhibit important lesions of diabetic retinopathy. This agent has potential for preventing retinopathy in patients with diabetes.
Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis
Background and purpose: We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology.
Experimental approach: STZ-induced diabetic rats were treated with or without LR-90 (50 mg L(-1) in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra.
Key results: LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats.
Conclusions and implications: Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications.