DT-Web

DB01276 - Exenatide


Identification
Name Exenatide
Accession Number DB01276
Type biotech
Description Exenatide, derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern US, is a functional analog of Glucagon-Like Peptide-1 (GLP-1), a naturally occuring peptide.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 4186.6000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control.
Mechanism of action Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals.
Absorption Following subcutaneous administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2.1 hours.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Nonclinical studies have shown that exenatide is predominantly eliminated by glomerular filtration with subsequent proteolytic degradation.
Toxicity Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Azilsartan medoxomil Pharmacodynamic synergist- increases effects. May also increase hypoglycemic effects by improving insulin sensitivity.
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of exenatide. Monitor for changes in fasting and postprandial blood sugars.
Food Interactions Not Available

Targets


Glucagon-like peptide 1 receptor
Name Glucagon-like peptide 1 receptor
Gene Name GLP1R
Pharmacological action yes
Actions agonist
References
  • Briones M, Bajaj M: Exenatide: a GLP-1 receptor agonist as novel therapy for Type 2 diabetes mellitus. Expert Opin Pharmacother. 2006 Jun;7(8):1055-64. - Pubmed
  • Hargrove DM, Kendall ES, Reynolds JM, Lwin AN, Herich JP, Smith PA, Gedulin BR, Flanagan SD, Jodka CM, Hoyt JA, McCowen KM, Parkes DG, Anderson CM: Biological activity of AC3174, a peptide analog of exendin-4. Regul Pept. 2007 Jun 7;141(1-3):113-9. Epub 2007 Jan 11. - Pubmed
  • Wajchenberg BL: beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev. 2007 Apr;28(2):187-218. Epub 2007 Mar 12. - Pubmed
  • Mack CM, Moore CX, Jodka CM, Bhavsar S, Wilson JK, Hoyt JA, Roan JL, Vu C, Laugero KD, Parkes DG, Young AA: Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures. Int J Obes (Lond). 2006 Sep;30(9):1332-40. Epub 2006 Mar 14. - Pubmed
  • Geelhoed-Duijvestijn PH: Incretins: a new treatment option for type 2 diabetes? Neth J Med. 2007 Feb;65(2):60-4. - Pubmed
  • Mann RJ, Nasr NE, Sinfield JK, Paci E, Donnelly D: The major determinant of exendin-4/glucagon-like peptide 1 differential affinity at the rat glucagon-like peptide 1 receptor N-terminal domain is a hydrogen bond from SER-32 of exendin-4. Br J Pharmacol. 2010 Aug;160(8):1973-84. - Pubmed
  • Degn KB, Brock B, Juhl CB, Djurhuus CB, Grubert J, Kim D, Han J, Taylor K, Fineman M, Schmitz O: Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes. 2004 Sep;53(9):2397-403. - Pubmed
  • Diamant M, Bunck MC, Heine RJ: [Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2] Ned Tijdschr Geneeskd. 2004 Sep 25;148(39):1912-7. - Pubmed
  • Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman MS, Baron AD: Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm. 2005 Jan 15;62(2):173-81. - Pubmed
  • Barnett AH: Exenatide. Drugs Today (Barc). 2005 Sep;41(9):563-78. - Pubmed
  • Lebovitz HE: Therapeutic options in development for management of diabetes: pharmacologic agents and new technologies. Endocr Pract. 2006 Jan-Feb;12 Suppl 1:142-7. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.1111

Predictions


Id Partner name Gene Name Score
584 Glucagon receptor GCGR 0.2376
3857 Glucagon-like peptide 2 receptor GLP2R 0.206
294 Neprilysin MME 0.1554
952 Dipeptidyl peptidase 4 DPP4 0.1069
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