| CAS |
No.320367-13-3 |
| 中文名称 |
利西拉来 |
| 英文名称 |
Lixisenatide |
| 别名 |
Lyxumia;Adlyxin;ZP10A peptide;AVE0010 |
| 分子式 |
C215H347N61O65S |
| 分子量 |
4858.49 |
| 溶解性 |
Soluble in Water ≥10mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD13194768 |
| SMILES |
CCC(C)C(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(=O)N)C(=O)NCC(=O)NCC(=O)N3CCCC3C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N4CCCC4C(=O)N5CCCC5C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)N)NC(=O)C(CC6=CC=CC=C6)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)C)NC(=O)C(C)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCSC)NC(=O)C(CCC(=O)N)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)CNC(=O)C(CC8=CNC=N8)N |
| 靶点 |
Glucagon Receptor |
| 通路 |
GPCR & G Protein |
| 背景说明 |
是胰高血糖素样肽 1 受体 (GLP-1R) 的激动剂,可用于2 型糖尿病的相关研究。 |
| 生物活性 |
Lixisenatide is a GLP-1 receptor agonist. Lixisenatide inhibits the inflammatory response through down regulation of proinflammatory cytokines， and blocks of cellular signaling pathways. Lixisenatide decreases atheroma plaque size and instability in Apoe?/? Irs2+/? mice by reprogramming macrophages towards an M2 phenotype， which leads to reduced inflammation[2][3][5]. |
| In Vitro |
To our knowledge， this is the first study exploring the effects of agonism of the glucagon - like peptide - 1 (GLP - 1) receptor using lixisenatide， a licensed drug used for the treatment of type II diabetes， on the pathological characteristics of RA in human fibroblast - like synoviocytes. Our findings indicate that lixisenatide inhibited the inflammatory response through downregulation of proinflammatory cytokines， such as tumor necrosis factor α (TNF - α)， interleukin - 6 (IL - 6)， and interleukin - 8 (IL - 8); inhibition of matrix metalloproteinases (MMPs); and blockade of cellular signaling pathways， including the c - Jun N - terminal kinase (JNK)， activator protein 1 (AP - 1)， and nuclear factor κ B (NF - κB) pathways. Furthermore， lixisenatide improved oxidative stress， rescued mitochondrial membrane potential (ΔΨm)， and prevented cell death in fibroblast - like synoviocytes.[3]Cell Viability Assay[1]：Cell Line:Hippocampal cells；Concentration:100 μM；Incubation Time:24 h；Result:Reversed Aβ25-35-triggered cytotoxicity on hippocampal cell cultures.Western Blot Analysis[3]：Cell Line:FLSs；Concentration:10 μM， 20 μM；Incubation Time:48 h；Result:Significantly reduced expression of MMP-1， MMP-3， and MMP-13 at both the mRNA and protein levels in a dose-dependent manner. |
| In Vivo |
Atherosclerosis development was evaluated in Apoe -/- Irs2 +/- mice， a mouse model of insulin resistance， the metabolic syndrome and atherosclerosis， treated with the GLP - 1 analogues lixisenatide or liraglutide.Treatment of Apoe -/- Irs2 +/- mice with either lixisenatide or liraglutide improved glucose metabolism and blood pressure but this was independent of body weight loss. Both drugs significantly decreased atheroma plaque size. Compared with vehicle - treated control mice， lixisenatide treatment generated more stable atheromas， with fewer inflammatory infiltrates， reduced necrotic cores and thicker fibrous caps. Lixisenatide - treated mice also displayed diminished IL - 6 levels， proinflammatory Ly6Chigh monocytes and activated T cells.Furthermore， atheromas from lixisenatide - treated mice showed higher arginase I content and decreased expression of inducible nitric oxide synthase， indicating the prevalence of the M2 phenotype within plaques.[2]。Animal Model: Apoe?/? Irs2+/? mice [2]；Dosage: 10 μg/kg；Administration:Subcutaneous injection (s.c.)；Result:Exhibited smaller atheromas in the aortic arch region.Reduced the lesion size in cross-sections of hearts.Animal Model:Diabetic rats [4]；Dosage:1 nmol/kg；Administration:Intraperitoneal injection (i.p.)；Result:Showed a significant amelioration on the elevated renal parameters.Showed significant mitigation in renal MDA and total NOx? (by 50.3 and 79.9%， respectively) and 43.9% elevation in renal total antioxidant capacity.Averted the observed increments in iNOS and COX-2 expressions in the renal tissues of the diabetic group.Decreased the level of TGF-β protein expression. |
| 数据来源文献 |
[1]. Cai H Y， et al. Lixisenatide attenuates the detrimental effects of amyloid β protein on spatial working memory and hippocampal neurons in rats [J]. Behavioural brain research， 2017， 318: 28-35.
[2]. Vinué á， et al. The GLP-1 analogue lixisenatide decreases atherosclerosis in insulin-resistant mice by modulating macrophage phenotype [J]. Diabetologia， 2017， 60: 1801-1812.
[3]. Du X， et al. The protective effects of lixisenatide against inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes [J]. International immunopharmacology， 2019， 75: 105732.
[4]. Abdel-Latif R G， et al. Low-dose lixisenatide protects against early-onset nephropathy induced in diabetic rats [J]. Life Sciences， 2020， 263: 118592.
[5]. Xiao M， et al. The protective effects of GLP-1 receptor agonist lixisenatide on oxygen-glucose deprivation/reperfusion (OGD/R)-induced deregulation of endothelial tube formation [J]. RSC advances， 2020， 10(17): 10245-10253.
[6]. Ahrén B et al. Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis. Diabetes Ther. 2016 Jun 18
[7]. Ulrich Werner， et al. Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes. Regul Pept. 2010 Sep 24;164(2-3):58-64.
[8]. Lorenz M， et al. Effects of lixisenatide once daily on gastric emptying in type 2 diabetes--relationship to postprandial glycemia. Regul Pept. 2013 Aug 10;185:1-8.
[9]. Mikkel Christensen， et al. Lixisenatide， a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. IDrugs. 2009 Aug;12(8):503-13.
[10]. D Tews， et al. Enhanced protection against cytokine- and fatty acid-induced apoptosis in pancreatic beta cells by combined treatment with glucagon-like peptide-1 receptor agonists and insulin analogues. Horm Metab Res. 2008 Mar;40(3):172-80. |
| 规格 |
1mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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