Selective neuropeptide y2 receptor agonists
This invention provides peptides that act as selective NPY2 receptor agonists in vitro and are efficacious in vivo to reduce food intake. The invention is a peptide selected from a specific group of derivatized NPY-related peptides, or functional equivalents thereof. The invention is also directed to a method of treating a metabolic disease in a mammal comprising administering a therapeutically effective amount of the peptides to said mammal to reduce food intake and body weight.
1 . A peptide of Formula (I)
Z-RHYLNLVTRQRY-NH 2
(SEQ ID NO: 1)
(I)
wherein
Z is selected from
2 . A peptide of Formula (II)
Z-HYLNLVTRQRY-NH 2
(SEQ ID NO:2)
(II)
wherein
Z is selected from
3 . A peptide of Formula (III)
Z-YLNLVTRQRY-NH 2
(SEQ ID NO:3)
(III)
wherein
Z is selected from
4 . A peptide of Formula (IV)
Z-LNLVTRQRY-NH 2
(SEQ ID NO:4)
(IV)
wherein
Z is selected from
5 . A peptide of Formula (V)
Z-NLVTRQRY-NH 2
(SEQ ID NO:5)
(V)
wherein
Z is selected from
6 . The peptide of any one of claims 1 to 5 , wherein said peptide is PEGylated.
7 . A pharmaceutical composition comprising a therapeutically effective amount of a peptide of any one of claims 1 to 5 , in combination with a pharmaceutically acceptable carrier.
8 . A pharmaceutical composition comprising a therapeutically effective amount of a peptide of any one of claims 1 to 5 , in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents.
9 . The pharmaceutical composition of claim 8 , wherein said pharmaceutical agent is an anti-obesity agent selected from the group consisting of β-3 agonists, CB-1 antagonists, appetite suppressants, and lipase inhibitors.
10 . The pharmaceutical composition of claim 8 , wherein said pharmaceutical agent is an agent for the treatment of diabetes selected from the group consisting of insulin, insulin derivatives, PPAR ligands, sulfonylurea drugs, α-glucosidase inhibitors, biguanides, PTP-1B inhibitors, DPP-IV inhibitors, 11-beta-HSD inhibitors, GLP-1 and GLP-1 derivatives, GIP and GIP derivatives, PACAP and PACAP derivatives, and secretin and secretin derivatives.
11 . The pharmaceutical composition of claim 8 , wherein said pharmaceutical agent is an agent for the treatment of lipid disorders selected from the group consisting of HMG-CoA inhibitors, nicotinic acid, fatty acid lowering compounds, lipid lowering drugs, ACAT inhibitors, bile sequestrants, bile acid reuptake inhibitors, microsomal triglyceride transport inhibitors, and fibric acid derivatives.
12 . The pharmaceutical composition of claim 8 , wherein said pharmaceutical agent is an anti-hypertensive agent selected from the group consisting of β-blockers, calcium channel blockers, diuretics, renin inhibitors, ACE inhibitors, AT-1 receptor antagonists, ET receptor antagonists, and nitrates.
13 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a peptide of any one of claims 1 to 5 or a composition of claim 7 .
14 . A method of inducing weight loss comprising the step of administering to a subject in need thereof a therapeutically effective amount of a peptide of any one of claims 1 to 5 or a composition of claim 7 .
15 . A method of preventing weight gain comprising the step of administering to a subject in need thereof a therapeutically effective amount of a peptide of any one of claims 1 to 5 or a composition of claim 7 .
16 . A method of treating obesity-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a peptide of any one of claims 1 to 5 or a composition of claim 7 .
17 . The method of claim 16 , wherein said obesity-related disorder is selected from the group consisting of dyslipidemia, cholesterol gallstones, gallbladder disease, gout, cancer, menstrual abnormalities, infertility, polycystic ovaries, osteoarthritis, sleep apnea, hypertriglyceridemia, Syndrome X, type 2 diabetes, atherosclerotic diseases, hyperlipidemia, hypercholesteremia, low HDL levels, hypertension, cardiovascular disease, coronary heart disease, coronary artery disease, cerebrovascular disease, stroke, and peripheral vessel disease.
18 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a peptide of any one of claims 1 to 5 in combination with one or more pharmaceutical agents.
19 . The method of claim 18 , wherein the peptide of any one of claims 1 to 5 and one or more pharmaceutical agents are administered as a single pharmaceutical dosage formulation.
20 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition of claim 8 , 9 , 10 , 11 , or 12 .
21 . A method of treating obesity-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition of claim 8 , 9 , 10 , 11 , or 12 .
22 . Peptides according to any one of claims 1 to 5 for the treatment and/or prophylaxis of obesity and obesity-related disorders.
23 . (canceled)
24 . (canceled)
25 . (canceled)