US 2014/0179604 A1Published application

Ghrh agonists for the treatment of ischemic disorders

AssigneesU.S.A., Represented By the Department of Veterans Affairs, University of Miami

InventorsAndrew V. SCHALLY, Joshua M. HARE, Norman L. BLOCK, Samirah A. GOMES, Rosemeire M. KANASHIRO-TAKEUCHI

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Abstract

Disclosed herein are compositions of GHRH agonists and peptides, and methods to treat disorders, such as ischemia and reperfusion injury. In one embodiment, a method of treating a reperfusion injury in a subject in need may involve administering a therapeutically effective amount of at least one GHRH agonist peptide to the subject. In additional embodiment, a method of promoting vasculogenesis in a mammal may involve administering a therapeutically effective amount of at least one GHRH agonist peptide to the subject. In a further embodiment, a method of promoting differentiation of mesenchymal stem cells into endothelial cells may involve contacting mesenchymal stem cells with at least one GHRH agonist peptide.

Claims21

Dependent claims

A method of treating a reperfusion injury in a subject in need thereof comprising administering a therapeutically effective amount of a GHRH agonist peptide to the subject, wherein the GHRH agonist peptide has the following formula:

[R1-A1-A2-Asp-Ala-Ile-A6-Thr-A8-Ser-Tyr-A11-A12-Val-Leu-A15-Gln-Leu-Ser-Ala-A20-A21-A22-Leu-Gln-Asp-Ile-Nle27-A28-A29-A30]-R2,
wherein R1 is Ac, Tfa, or is absent,
A1 is Tyr, Dat, or N-Me-Tyr,
A2 is Ala, D-Ala, Abu, or D-Abu,
A6 is Phe or Fpa5,
A8 is Asn, Ala, Gln, Thr, or N-Me-Ala,
A11 is Arg, His, or Har,
A12 is Orn, or Lys(Me)2,
A15 is Abu or Ala,
A20 is Arg, His, or Har,
A21 is Orn, or Lys(Me)2,
A22 is Leu, or Orn,
A28 is Ser, or Asp,
A29 is Arg, Har, Agm, D-Arg, or D-Har,
A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,
R2 is —NH2, —NH—CH3, NH—CH2—CH3, —NH—CH3, —OH, —NHR3, —N(R3)2, or —OR3, wherein R3 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl,
and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO:
1 in at least one amino acid residue.

15 more elements

A method of promoting vasculogenesis in a subject, the method comprising administering a therapeutically effective amount of a GHRH agonist peptide to the subject, wherein the GHRH agonist peptide has the following formula:

[R1-A1-A2-Asp-Ala-Ile-A6-Thr-A8-Ser-Tyr-A11-A12-Val-Leu-A15-Gln-Leu-Ser-Ala-A20-A21-A22-Leu-Gln-Asp-Ile-Nle27-A28-A29-A30]-R2,
wherein R1 is Ac, Tfa, or is absent,
A1 is Tyr, Dat, or N-Me-Tyr,
A2 is Ala, D-Ala, Abu, or D-Abu,
A6 is Phe or Fpa5,
A8 is Asn, Ala, Gln, Thr, or N-Me-Ala,
A11 is Arg, His, or Har,
A12 is Orn, or Lys(Me)2,
A15 is Abu or Ala,
A20 is Arg, His, or Har,
A21 is Orn, or Lys(Me)2,
A22 is Leu, or Orn,
A28 is Ser, or Asp,
A29 is Arg, Har, Agm, D-Arg, or D-Har,
A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,
R2 is —NH2, —NH—CH3, NH—CH2—CH3, —NH—CH3, —OH, —NHR3, —N(R3)2, or —OR3, wherein R3 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl,
and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO:
1 in at least one amino acid residue.

15 more elements

A method of promoting differentiation of mesenchymal stem cells into endothelial cells, the method comprising contacting the mesenchymal stem cells with a GHRH agonist peptide having the following formula:

[R1-A1-A2-Asp-Ala-Ile-A6-Thr-A8-Ser-Tyr-A11-A12-Val-Leu-A15-Gln-Leu-Ser-Ala-A20-A21-A22-Leu-Gln-Asp-Ile-Nle27-A28-A29-A30]-R2,
wherein R1 is Ac, Tfa, or is absent,
A1 is Tyr, Dat, or N-Me-Tyr,
A2 is Ala, D-Ala, Abu, or D-Abu,
A6 is Phe or Fpa5,
A8 is Asn, Ala, Gln, Thr, or N-Me-Ala,
A11 is Arg, His, or Har,
A12 is Orn, or Lys(Me)2,
A15 is Abu or Ala,
A20 is Arg, His, or Har,
A21 is Orn, or Lys(Me)2,
A22 is Leu, or Orn,
A28 is Ser, or Asp,
A29 is Arg, Har, Agm, D-Arg, or D-Har,
A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,
R2 is —NH2, —NH—CH3, NH—CH2—CH3, —NH—CH3, —OH, —NHR3, —N(R3)2, or —OR3, wherein R3 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl,
and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO:
1 in at least one amino acid residue.

15 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/138,391Filed 23 Dec 2013
Priority: 21 Dec 2012
Published: 26 Jun 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

A61K 38/16
Medicinal preparations containing peptides: peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A61K 38/25
Hormones: growth hormone-releasing factor [GH-RF], i.e. somatoliberin
C07K 14/60
Hormones: growth hormone-releasing factor [GH-RF], i.e. somatoliberin
A61K
Medicines and medical preparations