Colesevelam hydrochloride
Based on 1 Customer Validation
Colesevelam hydrochloride is an orally active bile acid sequestrant, lipid-lowering agent, and glycemic control agent. Colesevelam hydrochloride binds bile acids in the gastrointestinal tract to form nonabsorbable complexes, interrupts enterohepatic recirculation and increases fecal bile acid elimination. Colesevelam hydrochloride modulates FXR, TGR5, and Cyp7a1 activity and triggers cAMP signaling and GLP-1 release. Colesevelam hydrochloride alters hepatic lipid and glucose metabolism, suppresses hepatic glycogenolysis, reduces hepatic triglyceride and cholesterol levels, and increases LDL-C (low-density lipoprotein cholesterol) clearance. Colesevelam hydrochloride can be used for the research of type 2 diabetes mellitus, hypercholesterolemia, and alcohol-related liver disease.
For research use only. We do not sell to patients.
- Purity: 95.0%
- CAS No.: 182815-44-7
- Formula: (C3H8NCl)2.(C9H20N2OCl2).(C13H28NCl)7.(C12H28N2Cl2)6
- Molecular Weight:3694.64
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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PKA |
Colesevelam hydrochloride (5 mg/mL; 45 min incubation with taurocholic acid and oleic acid, followed by real-time cell treatment) forms a complex with taurocholic acid that activates human TGR5-mediated cAMP signaling in HEK293 TGR5-BRET cells, demonstrating that bile acids bound to Colesevelam hydrochloride retain TGR5 agonist activity[1].
Colesevelam hydrochloride (1 h) maintains stable bile acid binding affinity and capacity after suspension in common beverages, exhibits greater total bile acid binding (including higher affinity for GC) than traditional bile acid sequestrants under physiological conditions, and is four to six times as potent as these traditional agents[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Colesevelam hydrochloride (rectal) complexed with taurocholic acid is sufficient to induce GLP-1 release in normal mice[1].
Colesevelam hydrochloride (2%; oral; daily; from day 6 until study end) treatment mitigates ethanol-induced liver steatosis in humanized gnotobiotic mice by reducing hepatic lipid accumulation and related gene expression, but significantly increases serum liver injury markers and does not improve intestinal barrier function[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57Bl/6J wild-type (male);[1]
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Dosage:2%
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Administration:oral; ad libitum; 7 days
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Result:Normalized hepatic cholesterol levels.
Reduced fed plasma glucose concentrations and glucose excursion during glucose tolerance tests.
Alleviated hyperinsulinemia in diet-induced obese mice.
Decreased basal endogenous glucose production by suppressing hepatic glycogenolysis without altering gluconeogenic flux.
Elevated hepatic glycogen content in fed wild-type mice.
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Animal Model:TGR5 knockout (male); FXR knockout (male)[1]
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Dosage:2%
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Administration:oral; ad libitum; 7 days
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Result:Increased portal GLP-1 levels in wild-type lean and obese mice but not in TGR5-knockout mice.
Blocked the suppression of hepatic glycogenolysis and attenuated glucose lowering when coadministered with the GLP-1 receptor antagonist exendin-(9–39).
Retained the ability to reduce hyperinsulinemia despite GLP-1 receptor inhibition.
Reduced hepatic cholesterol levels in both wild-type and TGR5-knockout mice.
Induced hepatic expression of the cholesterol biosynthetic genes Cyp7a1 and Hmgcs.
Increased de novo cholesterol synthesis by sevenfold.Moderately reduced plasma insulin and decreased plasma glucose similarly in FXR-knockout mice.
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Animal Model:C57BL/6 (female, 5-6 weeks old, germ-free, colonized with feces from alcoholic hepatitis patients, chronic-binge ethanol feeding model)[2]
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Dosage:2% (by dry powder weight)
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Administration:oral; daily; from day 6 until study end
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Result:Reduced hepatic triglyceride and cholesterol levels.
Reduced hepatic mRNA expression of lipogenic and cholesterol synthesis genes (Acc1, Fasn, Hmgcr, Srebp1c) and ethanol-metabolizing genes (Adh1, Cyp2e1).
Reduced hepatic Cyp7a1 protein and Cyp27a1 mRNA expression.
Reduced hepatic Mpo (neutrophil marker) mRNA expression.
Significantly increased serum ALT and ALP levels.
Did not reduce serum bile acid levels, nor improve intestinal barrier function (serum LPS levels unchanged).
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 182815-44-7
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Appearance Solid
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Molecular Weight 3694.64
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Formula (C3H8NCl)2.(C9H20N2OCl2).(C13H28NCl)7.(C12H28N2Cl2)6
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Color White to light yellow
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SMILES
[Colesevelam (hydrochloride)]
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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Data Sheet (275 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Potthoff MJ, et al. Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice. Am J Physiol Gastrointest Liver Physiol. 2013;304(4):G371-G380. [Content Brief]
[2]. Cabré N, et al. Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice. Cells. 2021;10(6):1496. Published 2021 Jun 14. [Content Brief]
[3]. Younk LM, et al. Evaluation of colesevelam hydrochloride for the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol. 2012;8(4):515-525. [Content Brief]
[4]. Steinmetz KL, et al. Colesevelam hydrochloride. Am J Health Syst Pharm. 2002;59(10):932-939. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Colesevelam hydrochloride Related Classifications
HY-106539 Related Classifications
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