Cyclic peptidomimetic for the treatment of neurological disorders

Patent metadata

Field	Value
Publication number	US-11879020-B2
Application number	US-202217690809-A
Country	US
Kind code	B2
Filing date	Mar 9, 2022
Priority date	Oct 2, 2019
Publication date	Jan 23, 2024
Grant date	Jan 23, 2024

Abstract

The present invention provides to compositions and methods useful in the treatment of neurological disorders including, but not limited to, Angelman syndrome, depression, traumatic brain injury, stroke, and Alzheimer's disease. CN2097, a rationally designed cyclic peptidomimetic drug that has been demonstrated to have effectiveness in preclinical models for the treatment of neurological disorders, is rapidly cleared and has a short half-life. The present invention provides a stable analog of CN2097.

First claim

What is claimed is:

1. A method of treating a neurological disorder in a subject afflicted with the neurological disorder comprising administering a composition comprising (a) a therapeutically-effective amount of dR 7 -2097 and (b) at least one pharmaceutically-acceptable carrier,
wherein the dR 7 -2097 comprises RRRRRRRC (SEQ ID NO: 2 or PolyArg) in the following dR 7 -2097 structure:

wherein the PolyArg consists of all the R enantiomer, (R)-Arg or (“R”)-arginine, and all the S enantiomer, (“S”)-cysteine amino acids in the RRRRRRRC (SEQ ID NO: 2);
wherein in dR 7 -2097 there is a disulfide linkage from the (S)-Cys or (“S”)-cysteine to one (R)-Cys or (“R”)-cysteine;
wherein the PolyArg is operative to transport the dR 7 -2097 across the blood-brain barrier (BBB) in the subject, and the dR 7 -2097 is at least four times more efficacious than CN2097 in treating the neurological disorder; and wherein the neurogical disorder is major depressive disorder.

Assignees

• Univ Brown

Inventors

• Marshall John

Classifications

• C07K7/52 Primary

  with only normal peptide links in the ring · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P25/24 Primary

  Antidepressants · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title