Agonist of spexin-based galanin type 2 receptor and use thereof

Patent metadata

Field	Value
Publication number	US-2018319841-A1
Application number	US-201615771078-A
Country	US
Kind code	A1
Filing date	Nov 30, 2016
Priority date	Nov 30, 2015
Publication date	Nov 8, 2018
Grant date	—

Abstract

The present invention relates to spexin-based agonists specific for galanin receptor type 2 and use thereof. More specifically, the present invention provides peptide-based agonists with high specificity for galanin receptor type 2 and improved stability. The peptide-based agonists are involved in the regulation of in vivo physiological functions, such as food intake, anxiety, emotion, and addiction, for which galanin receptors type 2 is responsible, to effectively suppress appetite, help recover from anxiety disorder, and reduce pleasure addiction. Therefore, the peptide-based agonists can be used to prevent or treat galanin receptor type 2-mediated diseases.

First claim

1 . A peptide-based galanin receptor type 2 (GALR2) agonist having the amino acid sequence set forth in formula 1:
[ d N] 1 [W] 2 [T] 3 [P] 4 [N] 5 [A] 6 [A] 7 [L] 8 [Y] 9 [L] 10 [F] 11 [G] 12 [P] 13 [Q] 14 -NH 2   (1)
wherein one or more amino acids in formula 1 are optionally substituted, and wherein [A] 7 is alanine (A) and [F] 11 is phenylalanine (F).

2 . The peptide-based galanin receptor type 2 (GALR2) agonist according to claim 1 , wherein the agonist has any one of the amino acid sequences set forth in formulas 2 to 4:

(2)

dNWTPNAALYLFGPQ-NH 2

(3)

PEG-NWTdANAALYLFGPdQ-NH 2

(4)

Fmoc-NWTdANAALYLFGPdQ-NH 2

3 . The peptide-based galanin receptor type 2 (GALR2) agonist according to claim 1 , wherein the agonist does not activate galanin receptor type 1 (GALR1) and galanin receptor type 3 (GALR3) but specifically activates galanin receptor type 2 (GALR2).

4 . A composition for preventing or treating a galanin receptor type 2-mediated disease comprising the peptide-based galanin receptor type 2 agonist according to claim 1 .

5 . The composition according to claim 4 , wherein the galanin receptor type 2-mediated disease is attention deficit hyperactivity disorder (ADHD), bipolar disorder, body dysmorphic disorder, bulimia nervosa and other eating disorders, cataplexy, dysthymia, general anxiety disorder, hypersexuality, irritable bowel syndrome, impulse-control disorder (MDD), kleptomania, migraine, major depressive disorder, narcolepsy, obsessive-compulsive disorder, oppositional-defiant disorder, panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), social anxiety disorder, chronic pain, intermittent explosive disorder, pathological gambling, personality disorder, pyromania, substance abuse and addiction, trichotillomania or Alzheimer's disease.

6 . The composition according to claim 4 , wherein the composition is prepared into an injectable freeze-dried powder or solution.

7 . A method for preventing or treating a galanin receptor type 2-mediated disease comprising administering a pharmaceutically effective amount of the composition according to claim 4 to a subject in need of such prevention or treatment.

8 . The method according to claim 7 , wherein the composition is prepared into a freeze-dried powder or injectable solution.

9 . The method according to claim 7 , wherein the galanin receptor type 2-mediated disease is attention deficit hyperactivity disorder (ADHD), bipolar disorder, body dysmorphic disorder, bulimia nervosa and other eating disorders, cataplexy, dysthymia, general anxiety disorder, hypersexuality, irritable bowel syndrome, impulse-control disorder (MDD), kleptomania, migraine, major depressive disorder, narcolepsy, obsessive-compulsive disorder, oppositional-defiant disorder, panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), social anxiety disorder, chronic pain, intermittent explosive disorder, pathological gambling, personality disorder, pyromania, substance abuse and addiction, trichotillomania or Alzheimer's disease.

10 . The peptide-based galanin receptor type 2 (GALR2) agonist according to claim 1 , wherein [N] 5 is L-asparagine (N), [A] 7 is A, and [F] 11 is F.

11 . The peptide-based galanin receptor type 2 (GALR2) agonist according to claim 1 , wherein [N] 5 is N, [A] 7 is A, [F] 11 is F, and [P] 13 is proline (P).

Assignees

• Univ Korea Res & Bus Found
• Neuracle Science Co Ltd

Inventors

• Seong Jae Young
• Hwang Jong-Ik
• Kim Dong-Hoon
• Son Gi Hoon
• Lee Yoo-Na
• Yun Seongsik
• Reyes-Alcaraz Arfaxad

Classifications

• A61K9/00

  Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)} · CPC title

• A61P25/24 Primary

  Antidepressants · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/22

  Anxiolytics · CPC title