CAS |
No.851199-59-2 |
英文名称 |
Linaclotide |
分子式 |
C59H79N15O21S6 |
分子量 |
1526.74 |
溶解性 |
Soluble in DMSO ≥5mg/mL;Soluble in Water ≥1mg/mL |
纯度 |
≥98% |
外观(性状) |
White to off-white Solid |
储存条件 |
Powder:-20℃,1 year;Insolvent(母液):-20℃,6 months;-80℃,1 year |
靶点 |
Guanylate Cyclase |
通路 |
Metabolic Enzyme&Protease |
背景说明 |
Linaclotide 是一种有效和选择性的鸟苷酸环化酶 C (guanylate cyclase C) 激动剂。 |
生物活性 |
Linaclotide is a potent and selective guanylate cyclase C agonist; developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic constipation.[1-2] |
In Vitro |
Linaclotide inhibits in vitro [125I]-STa binding to intestinal mucosal membranes from wt mice in a concentration-dependent manner. In contrast, [125I]-STa binding to these membranes from GC-C null mice is significantly decreased. After incubation in vitro in jejunal fluid for 30 min, linaclotide is completely degraded[1]. Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation; the drug is minimally absorbed into the systemic circulation[2]. |
In Vivo |
Pharmacokinetic analysis shows very low oral bioavailability (0.10%). In intestinal secretion and transit models, linaclotide exhibits significant pharmacological effects in wt, but not in GC-C null mice: induction of increased fluid secretion into surgically ligated jejunal loops is accompanied by the secretion of elevated levels of cyclic guanosine-3‘,5-monophosphate and accelerated gastrointestinal transit[1]. Linaclotide significantly increases weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with chronic constipation[2]. |
动物实验 |
Mice: To determine oral bioavailability, three groups (n=3) of female CD-1 mice receive linaclotide (8 mg/kg) intravenously (i.v.), while two groups (n=3) receive linaclotide (8 mg/kg) by gavage (p.o.). Blood is allowed to clot for 5 min, centrifuged at 13,000×g for 3 min, and the serum is collected and stored at ?80 °C until sample preparation and analysis by LC-MS/MS[1]. |
数据来源文献 |
[1]. Bryant AP, et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci. 2010 May 8;86(19-20):760-5. [2]. Love BL, et al. Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome. Am J Health Syst Pharm. 2014 Jul 1;71(13):1081-91. |
规格 |
1mg 2mg 5mg 10mg 25mg 50mg |
单位 |
瓶 |