Linaclotide - Guanylate Cyclase Agonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELinaclotideCat. No.: HY-17584CAS No.: 851199-59-2分式: CHNOS分量: 1526.74作靶点: Guanylate Cyclase作通路: GPCR/G Protein储存式: Powder -80C 2 years-20C 1 yearIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 H2O : 20 mg/mL (13.10 mM; Need ultras

2、onic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 0.6550 mL 3.2750 mL 6.5499 mL5 mM 0.1310 mL 0.6550 mL 1.3100 mL10 mM 0.0655 mL 0.3275 mL 0.6550 mL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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Linaclotide种有效和选择性的鸟苷酸环化酶C激动剂；开发于治疗便秘型肠易激综合症 (IBS-C) 和慢性便秘。体外研究Linaclotide inhi

3、bits in vitro 125I-STa binding to intestinal mucosal membranes from wt mice in aconcentration-dependent manner. In contrast, 125I-STa binding to these membranes from GC-C null miceis significantly decreased. After incubation in vitro in jejunal fluid for 30 min, linaclotide is completelydegraded 1.

4、Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEchloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thusincreasing the secretion of water into the lumen and improving d

5、efecation; the drug is minimally absorbedinto the systemic circulation 2.体内研究 Pharmacokinetic analysis shows very low oral bioavailability (0.10%). In intestinal secretion and transitmodels, linaclotide exhibits significant pharmacological effects in wt, but not in GC-C null mice: induction ofincrea

6、sed fluid secretion into surgically ligated jejunal loops is accompanied by the secretion of elevatedlevels of cyclic guanosine-3,5-monophosphate and accelerated gastrointestinal transit 1. Linaclotidesignificantly increases weekly spontaneous bowel movements and complete spontaneous bowel movements

7、(CSBMs) while reducing abdominal pain in patients with chronic constipation 2.PROTOCOLAnimal Mice: To determine oral bioavailability, three groups (n=3) of female CD-1 mice receive linaclotide (8 mg/kg)Administration 1 intravenously (i.v.), while two groups (n=3) receive linaclotide (8 mg/kg) by gav

8、age (p.o.). Blood is allowed toclot for 5 min, centrifuged at 13,000g for 3 min, and the serum is collected and stored at 80 C until samplepreparation and analysis by LC-MS/MS 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Bryant AP, et

9、al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in thegastrointestinal 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 Jul1;71(13):1081-91.McePdfHeightCaution: Product has not been fully validated for med