Product Name: Liraglutide
Synonym:Liraglutide;Glycine, L-histidyl-L-alanyl-L-alpha-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-alpha-aspartyl-L-valyl-L-seryl-L-seryl-L-tyrosyl-L-leucyl-L-alpha-glutamylglycyl-L-glutaminyl-L-alanyl-L-alanyl-N6-(N-(1-oxohexadecyl)-L-gamma-glutamyl)-L-lysyl-L-alpha-glutamyl-L-phenylalanyl-L-isoleucyl-L-alanyl-L-tryptophyl-L-leucyl-L-valyl-L-arginylglycyl-L-arginyl-;Liraglutida;Liraglutida [inn-spanish];Liraglutide [usan:inn];Liraglutidum;Liraglutidum [inn-latin];N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)glp-1-(7-37)-peptide
MF:C172H265N43O51
MW:3751.202
Product Category: GLP
Pharmacodynamic and Pharmacology Properties: Liraglutide is an acylated GLP-1 analogue that shares 97 % amino acid sequence homology to human endogenous GLP-1 (7–37). The single amino acid substitution of lysine with arginine at position 34 and the attachment of a C16 fatty acid chain to lysine at position 26 enables liraglutide to self-associate and form a heptameric structure, which delays absorption from the subcutaneous injection site and provides protection against degradation by DPP-4 enzyme and neutral endopeptidases. As a consequence, liraglutide has a much longer half-life than endogenous GLP-1 (&13 h vs. 1.5–2 min).
Liraglutide binds to and activates the GLP-1 receptor, which is a membrane bound cell-surface receptor coupled to adenyl cyclase by the stimulatory G-protein (Gs) in pancreatic b cells (but not in pancreatic a-cells) and is the target for endogenous GLP-1. This results in increased intracellular cyclic monophosphate and subsequent liraglutide dose-dependent insulin release in patients with elevated glucose levels. At the same time, liraglutide acts in a glucose-dependent manner to decrease inappropriately high glucagon secretion, thereby blocking the effects of glucagon on hepatic glucose output. In the presence of liraglutide, as blood glucose concentrations decrease, the secretion of insulin diminishes and blood glucose concentrations approach euglycaemia. In addition to these glucoregulatory mechanisms of action in patients with type 2 diabetes, liraglutide slightly delays gastric emptying, and reduces bodyweight and body fat mass by reducing hunger and lowering energy intake; these effects may contribute to the beneficial effects of liraglutide in patients with type 2-diabetes. As reviewed previously, in patients with type 2 diabetes and/or in preclinical studies, liraglutide dosedependently reduced glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and postprandial plasma glucose levels, with sustained improvements in glucose levels over a 24-h dosage interval. In addition, liraglutide increased insulin secretion, reduced postprandial glucagon secretion, improved surrogate measures of b-cell function, reduced systolic blood pressure (SBP) and improved some biomarkers of cardiovascular (CV) risk in patients with type 2 diabetes, including suppression of postprandial triglyceride and apolipoprotein B48 levels after a fat-rich meal. Improvements in glycaemic control and other efficacy outcomes in adult patients with type 2 diabetes receiving liraglutide monotherapy or add-on therapies to other antidiabetic drugs in large phase III trials.
Description: Approaches to treating T2DM, a disease characterized by the dual defect of islet cell dysfunction and insulin resistance, include agents that increase the secretion of insulin by the pancreas (secretagogues), agents that increase the sensitivity of target organs to insulin (sensitizers), and agents that decrease the glucose absorption rate from the gastrointestinal tract.Liraglutide, the GLP-1 receptor agonist to reach the market, possesses a 97% homology to GLP-1 with only two amino acid changes and the addition of a fatty acid side chain. Specifically, the lysine in position 34 has been replaced with an arginine, and the lysine in position 26 has been modified with a C16 acyl chain via a glutamoyl spacer. Liraglutide derives its resistance to DPP-4 degradation from its propensity to form micelles and to bind to albumin. Unlike its predecessor exenatide, which requires two daily subcutaneous injections before the first and last meals of the day, liraglutide is approved as a once-daily treatment regimen and may be used in combination with metformin or a sulfonylurea in patients with insufficient glycemic control with either monotherapy or combined dual therapy. It is also approved in combination with the dual therapy of metformin and a thiazolidinedione in patients with insufficient glycemic control. Liraglutide displayed a binding potency of 61 pM (EC50= 55 pM for GLP-1) for the cloned human GLP-1 receptor.
关键字: 原料药与中间体;
一般项目:第二类医疗器械销售;针纺织品及原料批发;服装复试批发;日用百货销售;家用电器销售;第一类医疗器械销售;化工产品销售(不含许可类化工产品);五金产品批发;计算机软硬件及辅助设备批发;化妆品批发;消毒剂销售(不含危险化学品);专用化学产品销售(不含危验化学品);个人卫生用品销售;金属材料售;医用口罩批发;日用口罩(非医用)销售;医护人员防护用品批发;卫生用品和一次性使用医疗用品销售;劳动保护用品确售;合成材料销售;饲料添加剂销售;药物检测仪器销售;制药专用设备销售;财务咨询;信息咨询服务(不含许可类信息咨询服务);技术服务、技术开发、技术咨询、技术交流、技术转让、技术推广;染料销售;卫生用品销售;建筑装饰材料销售;电子办公设备销售;针纺识品销售;贸易经纪;销售代理;国内贸易代理(除依法须经批准的项目外,凭营业执照依法自主开展经营活动)。许可项目∶食品经营(销售预包装食品);货物进出口;药品进出口;进出口代理;技术进出口(依法须经批准的项目,经相关部门批批准方可开展经营活动,具体经营项目以审批结果为准)。