Cxcr antagonistic peptides and uses thereof

Patent metadata

Field	Value
Publication number	US-2018311302-A1
Application number	US-201815962067-A
Country	US
Kind code	A1
Filing date	Apr 25, 2018
Priority date	Nov 25, 2013
Publication date	Nov 1, 2018
Grant date	—

Abstract

The present invention provides a novel class of medicament based on CXCR antagonistic peptides. Among other things, the present invention provides peptides, compositions and methods for treating diseases, disorders and conditions in which a CXCR mediated pathway is implicated. Compositions and methods for effective treatment of inflammation, stroke, traumatic brain injury, pancreatic cancer, and others are provided.

First claim

1 .- 31 . (canceled)

32 . A method of treating inflammation, comprising administering to a subject in need thereof a peptide of less than 60 amino acids containing the amino acid sequence proline-glycine-X (PGX), wherein X is any amino acid.

33 . The method of claim 32 , wherein X is not proline.

34 . The method of claim 32 , wherein the inflammation is associated with arthritis (including rheumatoid arthritis and juvenile rheumatoid arthritis,); vasculitis; multiple sclerosis; autoimmune thyroiditis; inflammatory bowel disease (IBD); Crohn's disease; inflammatory conditions of, the nervous system (e.g., Alzheimer's disease), liver (e.g., hepatitis), kidney (e.g., nephritis) and pancreas (e.g., pancreatitis); cardiovascular disorders (pulmonary fibrosis, idiopathic pulmonary fibrosis, reperfusion injury, acute vaso-occlusive crisis in sickle cell anemia); respiratory disorders, e.g., COPD (e.g., cystic fibrosis); and infectious disease (e.g., acute endocarditis, pericarditis); adult respiratory distress syndrome (ARDS); Chronic Obstructive Pulmonary disease (COPD); tumors or cancers (e.g., soft tissue or solid tumors), such as melanoma or prostate cancer; or transplant rejection (e.g. destruction of pancreatic islet cells in islet cell transplantation, delayed graft failure in kidney or other organ transplantation); acute and chronic graft versus host disease.

35 . The method of claim 32 , wherein the inflammation is associated with an acute inflammatory condition.

36 . The method of claim 32 , wherein the inflammation is associated with a chronic inflammatory condition.

37 . The method of claim 32 , wherein the inflammation is neuroinflammation associated with stroke.

38 . A method of treating stroke, comprising administering to a subject in need thereof a peptide of less than 60 amino acids containing the amino acid sequence proline-glycine-X (PGX), wherein X is any amino acid.

39 . The method of claim 38 , wherein X is not proline.

40 . A method of treating brain injury, comprising administering to a subject in need thereof a peptide of less than 60 amino acids containing the amino acid sequence proline-glycine-X (PGX), wherein X is any amino acid.

41 . The method of claim 40 , wherein X is not proline.

42 .- 52 . (canceled)

53 . A method of inhibiting a CXC receptor activity in a subject, comprising administering to a subject in need thereof a peptide of less than 60 amino acids containing the amino acid sequence proline-glycine-X (PGX), wherein X is any amino acid except proline.

54 . The method of claim 48 , wherein the CXC receptor is selected from CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, and/or CXCR7.

55 . The method of claim 54 , wherein the CXC receptor is CXCR1 or CXCR2.

56 . (canceled)

57 . The method of claim 32 , wherein the sequence of proline-glycine-X (PGX) is at the N-terminus.

58 . The method of claim 32 , wherein the peptide is acetylated or methylated at the N-terminus.

59 . The method of claim 32 , wherein the peptide has less than 6 amino acids.

60 . (canceled)

61 . The method of claim 32 , wherein the peptide has less than 4 amino acids.

62 . The method of claim 32 , wherein the peptide is the N-acetylated tripeptide ac-PGG.

63 . The method of claim 32 , wherein the peptide is PEGylated.

64 . The method of claim 32 , wherein the peptide contains a plurality of PGX repeats.

65 .- 66 . (canceled)

67 . The method of claim 64 , wherein the PGX repeats are tandem repeats.

68 .- 69 . (canceled)

70 . The method of claim 64 , wherein the peptide is administered intravenously, subcutaneously, orally, transdermally, intramuscularly, intraperitoneally, and/or by aerosol inhalation.

71 .- 86 . (canceled)

Assignees

• Stc Unm

Inventors

• Hill Jeff Wade

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title