Oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same
The present invention relates to a novel peptide showing more excellent activities on a glucagon like peptide-1 receptor and a glucagon receptor than native oxyntomodulin, and a composition for the prevention or treatment of obesity comprising the peptide as an active ingredient. Unlike native oxyntomodulin, the novel peptide of the present invention reduces food intake, suppresses gastric emptying, and facilitates lipolysis with reduced side-effects, and also shows excellent receptor-activating effects. Thus, it can be widely used in the treatment of obesity with safety and efficacy.
1. A peptide comprising the amino acid sequence of SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, or SEQ ID NO:28.
2. The peptide according to claim 1 , wherein Glu at position 16 and Lys at position 20, taken together, form a ring.
3. The peptide according to claim 1 , wherein Lys at position 12 and Glu at position 16, taken together, form a ring.
4. A pharmaceutical composition comprising the peptide of claim 1 as an active ingredient and a pharmaceutically acceptable carrier.
5. The pharmaceutical composition according to claim 4 , wherein the composition is administered alone or in combination or coincident with other pharmaceutical formulations, wherein said other pharmaceutical formulation is selected from the group consisting of a glucagon like peptide-1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a Melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an Amylin receptor agonist, a Ghrelin antagonist, and a Ghrelin receptor antagonist.
6. A pharmaceutical composition comprising the peptide of claim 2 as an active ingredient and a pharmaceutically acceptable carrier.
7. The pharmaceutical composition according to claim 6 , which further comprises another active ingredient selected from the group consisting of a glucagon like peptide-1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an amylin receptor agonist, a ghrelin antagonist, and a ghrelin receptor antagonist.
8. A pharmaceutical composition comprising the peptide of claim 3 as an active ingredient and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition according to claim 8 , which further comprises another active ingredient selected from the group consisting of a glucagon like peptide- 1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an amylin receptor agonist, a ghrelin antagonist, and a ghrelin receptor antagonist.
10. A method for inhibiting or treating obesity, comprising administering to a subject in need thereof the peptide of claim 1 .
11. The method of claim 10 , which further comprises administering another active ingredient selected from the group consisting of a glucagon like peptide-1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a Melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an Amylin receptor agonist, a Ghrelin antagonist, and a Ghrelin receptor antagonist.
12. A method for inhibiting or treating obesity, comprising administering to a subject in need thereof the composition of claim 4 .
13. The method of claim 12 , which further administering another pharmaceutical formulation, wherein said other pharmaceutical formulation is selected from the group consisting of a glucagon like peptide-1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a Melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an Amylin receptor agonist, a Ghrelin antagonist, and a Ghrelin receptor antagonist.
14. A method for treating obesity, comprising administering to a subject in need thereof the composition of claim 6 .
15. The method of claim 14 , which further comprises administering another active ingredient selected from the group consisting of a glucagon like peptide-1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an amylin receptor agonist, a ghrelin antagonist, and a ghrelin receptor antagonist.
16. A method for treating obesity, comprising administering to a subject in need thereof the composition of claim 8 .
17. The method of claim 16 , which further comprises administering another active ingredient selected from the group consisting of a glucagon like peptide-1 receptor agonist, a leptin receptor agonist, a dipeptidyl peptidase-IV inhibitor, a Y5 receptor antagonist, a melanin-concentrating hormone receptor antagonist, a Y2/3 receptor agonist, a MC3/4 receptor agonist, a gastric/pancreatic lipase inhibitor, a 5HT2c agonist, a β3A receptor agonist, an amylin receptor agonist, a ghrelin antagonist, and a ghrelin receptor antagonist.