Lead compound for otoprotection: targeting HGF signaling with dihexa

Patent metadata

Field	Value
Publication number	US-9475854-B2
Application number	US-201514720061-A
Country	US
Kind code	B2
Filing date	May 22, 2015
Priority date	May 23, 2014
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

A novel method of preventing or reducing ototoxicity in vertebrates undergoing treatment with therapeutically effective amounts of platinum-based chemotherapeutic agents such as cisplatin or aminoglycoside antibiotics is disclosed herein. The method(s) comprise administering an effective amount of an otoprotective agent comprising Dihexa prior to, concomitantly with, or subsequently to administration of the platinum-based chemotherapeutic agent or aminoglycoside antibiotic.

First claim

The invention claimed is:

1. A method of treating or preventing hearing loss a subject in need thereof, comprising:
administering to said subject one or more hepatocyte growth factor (HGF) mimics having formula

where
X═(CH 2 )m where m is 3-8, or a substituted or unsubstituted phenyl;
R 1 is a D or L cysteine, phenyalanine, aspartic acid, glutamic acid, serine, tyrosine, homocysteine, homoserine or homophenylalanine amino acid residue;
R 2 is a D or L isoleucine, leucine or valine amino acid residue; and
n ranges from 3-7;

and wherein covalent bonds 1, 2 and 3 are either peptide bonds or reduced peptide bonds.

2. The method of claim 1 , wherein said HGF mimic is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.

3. A method of protecting from ototoxic and noise induce damage and/or bringing about hair cell replacement in a subject in need thereof, comprising:
administering to said subject one or more hepatocyte growth factor (HGF) mimics having formula

where
X═(CH 2 )n where m is 3-8, or a substituted or unsubstituted phenyl;
R 1 is a D or L cysteine, phenyalanine, aspartic acid, glutamic acid, serine, tyrosine, homocysteine, homoserine or homophenylalanine amino acid residue;
R 2 is a D or L isoleucine, leucine or valine amino acid residue; and
n ranges from 3-7;

and wherein covalent bonds 1, 2 and 3 are either peptide bonds or reduced peptide bonds.

4. The method of claim 3 , wherein said HGF mimic is hexanoic-tyrosine-isoleucine-(6) amino hexanoic amide.

Assignees

• Coffin Allison
• Harding Joseph
• Kawas Leen
• Uribe Phillip
• Univ Washington State

Inventors

• Coffin Allison
• Harding Joseph
• Kawas Leen
• Uribe Phillip

Classifications

• C07K5/06078

  and aromatic or cycloaliphatic · CPC title

• C07K5/06104

  with the first amino acid being acidic · CPC title

• C07K14/4753 Primary

  Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II · CPC title

• C07K5/0606

  the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr · CPC title

• C07K5/06113

  Asp- or Asn-amino acid · CPC title