CA2515080A1 - Methods for preventing mitochondrial permeability transition - Google Patents

Methods for preventing mitochondrial permeability transition Download PDF

Info

Publication number
CA2515080A1
CA2515080A1 CA002515080A CA2515080A CA2515080A1 CA 2515080 A1 CA2515080 A1 CA 2515080A1 CA 002515080 A CA002515080 A CA 002515080A CA 2515080 A CA2515080 A CA 2515080A CA 2515080 A1 CA2515080 A1 CA 2515080A1
Authority
CA
Canada
Prior art keywords
peptide
amino acids
mammal
minimum
net positive
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002515080A
Other languages
French (fr)
Other versions
CA2515080C (en
Inventor
Hazel H. Szeto
Kesheng Zhao
Peter W. Schiller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Clinical Research Institute of Montreal
Cornell Research Foundation Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2515080A1 publication Critical patent/CA2515080A1/en
Application granted granted Critical
Publication of CA2515080C publication Critical patent/CA2515080C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/03—Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1019—Tetrapeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic

Abstract

The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids;
a relationship between the minimum number of net positive charges (pm) and the total number of amino acid residues (r) wherein 3pm is the largest number that is less than or equal to r + 1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (pt) wherein 2a is the largest number that is less than or equal to pt + 1, except that when a is 1, pt may also be 1.

Claims (57)

1. A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an aromatic-cationic peptide having:

(a) at least one net positive charge;
(b) a minimum of four amino acids;
(c) a maximum of about twenty amino acids;
(d) a relationship between the minimum number of net positive charges (p m) and the total number of amino acid residues (r) wherein 3p m is the largest number that is less than or equal to r + 1; and (e) a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t) wherein 2a is the largest number that is less than or equal to p t + 1, except that when a is 1, p t may also be 1.
2. The method according to claim 1, wherein 2p m is the largest number that is less than or equal to r+1.
3. The method according to claim 1, wherein a is equal to p t.
4. The method according to claim 1, wherein the peptide has a minimum of two positive charges.
5. The method according to claim 1, wherein the peptide has a minimum of three positive charges.
6. The method according to claim 1, wherein the peptide is water soluble.
7. The method according to claim 1, wherein the peptide comprises one or more D-amino acids.
8. The method according to claim 1, wherein the C-terminal carboxyl group of the amino acid at the C-terminus is amidated.
9. The method according to claim 1, wherein the peptide comprises one or more non-naturally occurring amino acids.
10. The method according to claim 1, wherein the peptide has a minimum of four amino acids.
11. The method according to claim 1, wherein the peptide has a maximum of about twelve amino acids.
12. The method according to claim 1, wherein the peptide has a maximum of about nine amino acids.
13. The method according to claim 1, wherein the peptide has a maximum of about six amino acids.
14. The method according to claim 1, wherein the peptide has mu-opioid receptor agonist activity.
15. The method according to claim 1, wherein the peptide does not have mu-opioid receptor agonist activity.
16. The method according to claim 15, wherein the peptide has the formula D-Arg-Dmt-Lys-Phe-NH2.
17. The method according to claim 14, wherein the peptide comprises a tyrosine residue at the N-terminus.
18. The method according to claim 17, wherein the peptide comprises a 2',6'-dimethyltyrosine residue at the N-terminus.
19. The method according to claim 15, wherein the peptide comprises a D-Arginine residue at the N-terminus.
20. The method according to claim 15, wherein the peptide comprises a phenylalanine residue at the N-terminus.
21. The method according to claim 20, wherein the peptide comprises a 2',6'-dimethylphenylalanine residue at the N-terminus.
22. The method according to claim 17, wherein the peptide has the formula Tyr-D-Arg-Phe-Lys-NH2 (DALDA).
23. The method according to claim 18, wherein the peptide has the formula 2',6'-Dmt-D-Arg-Phe-Lys-NH2 (Dmt1 -DALDA).
24. The method according to claim 20, wherein the peptide has the formula Phe-D-Arg-Phe-Lys-NH2 (Phe1 -DALDA).
25. The method according to claim 21, wherein the peptide has the formula 2',6'-Dmp-D-Arg-Phe-Lys-NH2 (Dmp1-DALDA).
26. The method according to claim 1, wherein the peptide is administered orally.
27. The method according to claim 1, wherein the peptide is administered topically.
28. The method according to claim 1, wherein the peptide is administered intranasally.
29. The method according to claim 1, wherein the peptide is administered systemically.
30. The method according to claim 27, wherein the peptide is administered intravenously.
31. The method according to claim 1, wherein the peptide is administered subcutaneously.
32. The method according to claim 1, wherein the peptide is administered intramuscularly.
33. The method according to claim 1, wherein the peptide is administered intracerebroventricularly.
34. The method according to claim 1, wherein the peptide is administered intrathecally.
35. The method according to claim 1, wherein the peptide is administered transdermally.
36. The method according to claim 35, wherein the transdermal administration is by iontophoresis.
]
37. The method according to claim 1, wherein the mammal is suffering from ischemia.
38. The method according to claim 1, wherein the mammal is suffering from reperfusion.
39. The method according to claim 1, wherein the mammal is suffering from hypoxia.
40 40. The method according to claim 37, wherein the ischemia is due to stroke.
41. The method according to claim 37, wherein the ischemia is intestinal ischemia.
42. The method according to claim 37, wherein the ischemia is present in a muscle tissue.
43. The method according to claim 42, wherein the muscle tissue is cardiac muscle tissue.
44. The method according to claim 42, wherein the muscle tissue is skeletal muscle tissue.
45. The method according to claim 42, wherein the muscle tissue is smooth muscle tissue.
46. The method according to claim 1, wherein the mammal is suffering from hypoxia.
47. The method according to claim 1, wherein the mammal is suffering from a neurodegenerative disease or condition.
48. The method according to claim 47, wherein the neurodegenerative disease or condition is Parkinson's disease.
49. The method according to claim 47, wherein the neurodegenerative disease or condition is Alzheimer's disease.
50. The method according to claim 47, wherein the neurodegenerative disease or condition is Huntington's disease.
51. The method according to claim 47, wherein the neurodegenerative disease or condition is Amyotrophic Lateral Sclerosis (ALS).
52. The method according to claim 1, wherein the mammal is suffering from drug-induced MPT.
53. The method according to claim 1, wherein the mammal is a human.
54. A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of an aromatic-cationic peptide having:
(a) at least one net positive charge;
(b) a minimum of four amino acids;
(c) a maximum of about twenty amino acids;
(d) a relationship between the minimum number of net positive charges (p m) and the total number of amino acid residues (r) wherein 3p m is the largest.
number that is less than or equal to r + 1; and (e) a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t) wherein 2a is the largest number that is Less than or equal to p t + 1, except that when a is 1, p t may also be 1.
55. A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT), or preventing mitochondria) permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an aromatic-cationic peptide having:
(a) at least one net positive charge;
(b) a minimum of three amino acids;
(c) a maximum of about twenty amino acids;

(d) a relationship between the minimum number of net positive charges (p m) and the total number of amino acid residues (r) wherein 3p m is the largest number that is less than or equal to r + 1; and (e) a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t) wherein 3a is the largest number that is less than or equal to p t + 1, except that when a is l, p t may also be 1.
56. A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of an aromatic-cationic peptide having:
(a) at least one net positive charge;
(b) a minimum of three amino acids;
(c) a maximum of about twenty amino acids;
(d) a relationship between the minimum number of net positive charges (p m) and the total number of amino acid residues (r) wherein 3p m is the largest number that is less than or equal to r + 1; and (e) a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t) wherein 3a is the largest number that is less than or equal to p t + 1, except that when a is 1, p t may also be 1.
57. A peptide having the sequence D-Arg-Dmt-Lys-Phe-NH2.
CA2515080A 2003-02-04 2004-02-03 Methods for preventing mitochondrial permeability transition Expired - Lifetime CA2515080C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US44477703P 2003-02-04 2003-02-04
US60/444,777 2003-02-04
US53569004P 2004-01-08 2004-01-08
US60/535,690 2004-01-08
PCT/US2004/003193 WO2004070054A2 (en) 2003-02-04 2004-02-03 Methods for preventing mitochondrial permeability transition

Publications (2)

Publication Number Publication Date
CA2515080A1 true CA2515080A1 (en) 2004-08-19
CA2515080C CA2515080C (en) 2012-04-10

Family

ID=32853391

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2515080A Expired - Lifetime CA2515080C (en) 2003-02-04 2004-02-03 Methods for preventing mitochondrial permeability transition

Country Status (14)

Country Link
US (8) US7576061B2 (en)
EP (9) EP3479838A1 (en)
JP (7) JP4838114B2 (en)
CN (3) CN102784383B (en)
AU (1) AU2004209663B2 (en)
CA (1) CA2515080C (en)
CY (2) CY1114959T1 (en)
DK (3) DK1599216T3 (en)
ES (3) ES2540897T3 (en)
HK (6) HK1090571A1 (en)
HU (1) HUE027110T2 (en)
PT (2) PT2656854E (en)
SI (1) SI2656854T1 (en)
WO (1) WO2004070054A2 (en)

Families Citing this family (59)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1599216T3 (en) * 2003-02-04 2013-12-09 Cornell Res Foundation Inc Method of preventing mitochondrial permeability transition
DK2604285T3 (en) 2003-05-01 2014-12-01 Cornell Res Foundation Inc Method and carrier complex for delivering molecules to cells
RU2376028C2 (en) * 2004-01-23 2009-12-20 Корнелл Рисеч Фаундейшн, Инк. Method for reduction of oxidising injury (versions)
AU2006292352B2 (en) * 2005-09-16 2012-02-09 Cornell Research Foundation, Inc. Methods for reducing CD36 expression
AU2014203126B2 (en) * 2005-09-16 2016-03-10 Cornell Research Foundation, Inc. Methods for reducing cd36 expression
EP2252312B1 (en) 2008-02-07 2014-04-09 Cornell University Methods for preventing or treating insulin resistance
CN106975070A (en) 2008-02-26 2017-07-25 康奈尔大学 Method for preventing and treating acute injury of kidney
DE102008061044A1 (en) 2008-12-11 2010-06-17 Henkel Ag & Co. Kgaa Composition with antioxidant peptides
EP3199173B1 (en) * 2009-03-20 2019-04-24 The General Hospital Corporation d/b/a Massachusetts General Hospital D-arg-2'6'-dimethyltyrosine-lys-phe-nh2 for use in the prevention and treatment of burn injuries
CA2770688C (en) * 2009-08-12 2018-06-05 Cornell University Methods for preventing or treating metabolic syndrome
EP2470191B1 (en) 2009-08-24 2014-05-07 Stealth Peptides International, Inc. Methods and compositions for preventing or treating ophthalmic conditions
CN103845724A (en) * 2009-10-05 2014-06-11 康奈尔大学 Methods for the prevention or treatment of heart failure
CN102791279A (en) * 2009-12-31 2012-11-21 康肽德生物医药技术有限公司 Methods for performing a coronary artery bypass graft procedure
AU2010339410A1 (en) * 2009-12-31 2012-07-19 Stealth Peptides International, Inc. Methods for the prevention or treatment of vessel occlusion injury
JP2013518057A (en) * 2010-01-25 2013-05-20 コーネル ユニヴァーシティー Aromatic cationic peptides and uses thereof
WO2011106717A1 (en) * 2010-02-26 2011-09-01 University Of Florida Research Foundation, Inc. Mitochondrial-targeted antioxidants protect against mechanical ventilation-induced diaphragm dysfunction and skeletal muscle atrophy
EP3210615A1 (en) * 2010-03-15 2017-08-30 Stealth Peptides International, Inc. Combination therapies using cyclosporine and aromatic cationic peptides
US20110245182A1 (en) * 2010-04-06 2011-10-06 Perricone Nicholas V Topical Uses of Szeto-Schiller Peptides
US20110245183A1 (en) * 2010-04-06 2011-10-06 Perricone Nicholas V Topical Uses of Szeto-Schiller Peptides
EP2942354A1 (en) * 2010-05-03 2015-11-11 Stealth Peptides International, Inc. Aromatic-Cationic Peptides and Uses of Same
EP2590664B1 (en) * 2010-07-09 2019-03-27 Stealth Peptides International, Inc. Methods for the prevention or treatment of no-reflow following ischemia/reperfusion injury
US20160176930A1 (en) 2010-07-09 2016-06-23 The Administrators Of The Tulane Educational Fund Mu opioid receptor agonist analogs of the endomorphins
WO2014137496A1 (en) * 2013-03-08 2014-09-12 The Administrators Of The Tulane Educational Fund Mu opioid receptor agonist analogs of the endomorphins
US20120083452A1 (en) * 2010-09-30 2012-04-05 Perricone Nicholas V Topical Anesthetic Uses of Szeto-Schiller Peptides
EP3108975A1 (en) * 2011-03-24 2016-12-28 Cornell University Aromatic-cationic peptides and uses of same
WO2013043580A2 (en) 2011-09-19 2013-03-28 Gencia Corporation Modified creatine compounds
US9988422B2 (en) * 2011-09-29 2018-06-05 Stealth Biotherapeutics Corp Aromatic-cationic peptides and methods for using same
EP2768516A4 (en) * 2011-10-17 2015-08-19 Univ Cornell Aromatic-cationic peptides and uses of same
EP3656394A1 (en) * 2011-12-09 2020-05-27 Stealth Peptides International, Inc. Aromatic-cationic peptides and uses of same
EP2830644B1 (en) * 2012-03-30 2016-11-16 Stealth Peptides International, Inc. Methods and compositions for the prevention and treatment neuropathy
CA2880643A1 (en) * 2012-08-02 2014-02-06 Stealth Peptides International, Inc. Methods for treatment of atherosclerosis
EP4005582A1 (en) * 2012-10-22 2022-06-01 Stealth BioTherapeutics Inc. Treatment of left ventricular remodeling
WO2014134554A1 (en) 2013-03-01 2014-09-04 Stealth Peptides International, Inc. Methods and compositions for the prevention or treatment of barth syndrome
WO2014134562A1 (en) * 2013-03-01 2014-09-04 Stealth Peptides International, Inc. Methods for the treatment of mitochondrial disease
US9850278B2 (en) 2013-04-25 2017-12-26 Carmel-Haifa University Economic Corp. Synthetic anti-inflammatory peptides and use thereof
WO2014209905A2 (en) 2013-06-26 2014-12-31 Stealth Peptides International, Inc. Methods and compositions for detecting and diagnosing diseases and conditions
WO2015017781A1 (en) * 2013-08-01 2015-02-05 Stealth Peptides International, Inc. Methods and compositions for preventing or treating leber's hereditary optic neuropathy
CA2920020C (en) 2013-08-02 2023-03-14 Stealth Biotherapeutics Corp Methods and compositions for the prevention and treatment of friedreich's ataxia
AU2014324580B2 (en) * 2013-09-30 2020-02-27 Cornell University Cardiolipin-targeted peptides inhibit beta-amyloid oligomer toxicity
US11491480B2 (en) 2014-06-13 2022-11-08 Children's Medical Center Corporation Products and methods to isolate mitochondria
ES2869430T3 (en) 2014-06-25 2021-10-25 Flamma Spa Procedure for preparing D-arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-L-phenylalaninamide
SI3160985T1 (en) 2014-06-30 2021-11-30 Flamma S.P.A. Process for the production of d-arginyl-2,6-dimethyl-l-tyrosyl-l-lysyl-l-phenylalaninamide
WO2016004093A2 (en) * 2014-07-01 2016-01-07 Stealth Biotherapeutics Corp Therapeutic compositions including galectin-3 inhibitors and uses thereof
CN104306954B (en) * 2014-09-25 2016-08-24 中山大学 WRY tripeptides purposes in preparation treatment Alzheimer disease drug
EP3212194A4 (en) 2014-10-29 2018-06-20 University Of Maryland Methods of treating age-related symptoms in mammals and compositions therefor
WO2017015660A1 (en) * 2015-07-23 2017-01-26 Salk Institute For Biological Studies Prevention and treatment of aging and neurodegenerative diseases
WO2017093897A1 (en) * 2015-11-30 2017-06-08 Peter Schiller Aromatic-cationic peptides conjugated to antioxidants and their use in treating complex regional pain syndrome
JP7038675B2 (en) 2016-03-11 2022-03-18 ステルス バイオセラピューティクス インコーポレイテッド Crystal salt morphology
CN109563131A (en) 2016-04-11 2019-04-02 卡诺有限责任公司 Chiral peptide
EP3550349A4 (en) 2016-11-30 2020-09-02 Daicel Corporation Lens module for imaging device, and method for producing lens module
EP3606938A1 (en) 2017-04-05 2020-02-12 Stealth BioTherapeutics Corp Crystalline salt forms of boc-d-arg-dmt-lys-(boc)-phe-nh2
WO2019033330A1 (en) 2017-08-17 2019-02-21 Xw Laboratories, Inc. Preparation and uses of reactive oxygen species scavenger derivatives
WO2019041361A1 (en) 2017-09-04 2019-03-07 Xw Laboratories, Inc. Preparation and use of reactive oxygen species scavenger
JP6958860B2 (en) * 2017-11-07 2021-11-02 学校法人自治医科大学 Agents for improving mitochondrial dysfunction, preventive or therapeutic agents for diseases or symptoms caused by mitochondrial dysfunction, and their uses
US10676506B2 (en) 2018-01-26 2020-06-09 Stealth Biotherapeutics Corp. Crystalline bis- and tris-hydrochloride salt of elamipretide
EP3898652A4 (en) * 2018-12-18 2022-08-24 Stealth BioTherapeutics Inc. Mitochondria-targeting peptides
US20220347212A1 (en) * 2019-05-02 2022-11-03 Children`S Medical Center Corporation Prophylactic and therapeutic use of mitochondria and combined mitochondrial agents
EP3771467A1 (en) 2019-07-30 2021-02-03 Fundacio Institut de Recerca de l'Hospital de la Santa Creu i sant Pau Ss-31 for the prevention and/or treatment of aneurysm
KR20230066428A (en) 2020-09-09 2023-05-15 소셜 프로핏 네트워크 Methods and compositions for delivery of biotin to mitochondria

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US5602100A (en) 1988-06-30 1997-02-11 Astra Ab Dermorphin analogs having pharmacological activity
SG64368A1 (en) 1988-06-30 1999-04-27 Astra Ab Dermorphin analogs their methods of preparation pharmaceutical compositions and methods of therapeutic treatment using the same
US5652122A (en) 1989-12-21 1997-07-29 Frankel; Alan Nucleic acids encoding and methods of making tat-derived transport polypeptides
DE69129294T2 (en) * 1990-01-17 1998-10-01 Univ California COMPOSITION TO IMPROVE LIFE CONSERVATION OF BIOLOGICAL MATERIALS
US5858784A (en) 1991-12-17 1999-01-12 The Regents Of The University Of California Expression of cloned genes in the lung by aerosol- and liposome-based delivery
US5716644A (en) 1992-06-11 1998-02-10 Alkermes, Inc. Composition for sustained release of non-aggregated erythropoietin
US5674534A (en) 1992-06-11 1997-10-07 Alkermes, Inc. Composition for sustained release of non-aggregated erythropoietin
IS4261A (en) 1994-02-21 1995-08-22 Astra Aktiebolag New peptide opioids for the treatment of pain and their use
EP0747092B1 (en) * 1995-06-09 2003-12-03 Hisamitsu Pharmaceutical Co., Inc. Matrix for iontophoresis
US5849761A (en) 1995-09-12 1998-12-15 Regents Of The University Of California Peripherally active anti-hyperalgesic opiates
HUP9904682A3 (en) * 1996-10-07 2001-09-28 Lilly Co Eli Phenyloxazole and -thiazole derivatives, their use and pharmaceutical compositions containing them
US5885958A (en) 1997-03-25 1999-03-23 Administrators Of The Tulane Educational Fund Mu-opiate receptor peptides
US5989463A (en) 1997-09-24 1999-11-23 Alkermes Controlled Therapeutics, Inc. Methods for fabricating polymer-based controlled release devices
CA2314267A1 (en) 1997-12-10 1999-06-17 Washington University Anti-pathogen system and methods of use thereof
JP2002512954A (en) * 1998-04-24 2002-05-08 マイトコー Compounds and methods for treating mitochondrial-related diseases
US6472378B2 (en) * 1998-08-31 2002-10-29 Pro-Neuron, Inc. Compositions and methods for treatment of mitochondrial diseases
US6245740B1 (en) 1998-12-23 2001-06-12 Amgen Inc. Polyol:oil suspensions for the sustained release of proteins
GB9905503D0 (en) * 1999-03-10 1999-05-05 Adprotech Plc Novel compound formulations and methods of delivery
SE9900961D0 (en) 1999-03-16 1999-03-16 Astra Ab Novel compounds
JP2003511045A (en) * 1999-10-04 2003-03-25 ユニバーシティー オブ メディシン アンド デンティストリー オブ ニュー ジャージー Method for identifying RNA-binding compounds
US6759520B1 (en) * 1999-10-28 2004-07-06 The New England Medical Center Hospitals, Inc. Chimeric analgesic peptides
US20050192215A1 (en) 2000-01-21 2005-09-01 Malabika Ghosh Methods and materials relating to novel polypeptides and polynucleotides
EP1303186B1 (en) 2000-07-18 2011-01-26 Cornell Research Foundation, Inc. Medicinal uses of mu-opioid receptor agonists
US6900178B2 (en) 2000-09-12 2005-05-31 University Of Kentucky Research Foundation Protection against ischemia and reperfusion injury
CA2430409A1 (en) * 2000-11-28 2002-06-06 Guilford Pharmaceuticals Inc. Bisubstituted carbocyclic cyclophilin binding compounds and their use
US6545097B2 (en) * 2000-12-12 2003-04-08 Scimed Life Systems, Inc. Drug delivery compositions and medical devices containing block copolymer
CA2435829A1 (en) * 2001-01-25 2002-08-01 Guilford Pharmaceuticals Inc. Trisubstituted carbocyclic cyclophilin binding compounds and their use
US20030077826A1 (en) * 2001-02-02 2003-04-24 Lena Edelman Chimeric molecules containing a module able to target specific cells and a module regulating the apoptogenic function of the permeability transition pore complex (PTPC)
DE60232710D1 (en) * 2001-02-16 2009-08-06 Cordis Corp METHOD FOR PRODUCING A BALLOON CATHETER STENT APPLICATION SYSTEM WITH FINISHING
JP2004526499A (en) * 2001-03-16 2004-09-02 エスティーエス バイオポリマーズ，インコーポレイティド Drug-loaded stent with multi-layer polymer coating
WO2002102833A1 (en) * 2001-06-15 2002-12-27 Senju Pharmaceutical Co., Ltd. Novel endomorphine derivatives
DK1599216T3 (en) * 2003-02-04 2013-12-09 Cornell Res Foundation Inc Method of preventing mitochondrial permeability transition
SI1599216T1 (en) * 2003-02-04 2014-02-28 Cornell Research Foundation, Inc. Methods for preventing mitochondrial permeability transition
DK2604285T3 (en) 2003-05-01 2014-12-01 Cornell Res Foundation Inc Method and carrier complex for delivering molecules to cells
JP2005005762A (en) * 2003-06-09 2005-01-06 Fujitsu Ltd Transmission power control method and apparatus
US7232824B2 (en) 2003-09-30 2007-06-19 Scios, Inc. Quinazoline derivatives as medicaments
RU2376028C2 (en) * 2004-01-23 2009-12-20 Корнелл Рисеч Фаундейшн, Инк. Method for reduction of oxidising injury (versions)
AU2006292352B2 (en) 2005-09-16 2012-02-09 Cornell Research Foundation, Inc. Methods for reducing CD36 expression

Also Published As

Publication number Publication date
HK1209652A1 (en) 2016-04-08
US20100190718A1 (en) 2010-07-29
WO2004070054A3 (en) 2005-04-14
HK1204999A1 (en) 2015-12-11
DK2656854T3 (en) 2015-07-06
US8404646B2 (en) 2013-03-26
AU2004209663B2 (en) 2009-01-15
CN102617706A (en) 2012-08-01
JP2017095519A (en) 2017-06-01
HUE027110T2 (en) 2016-08-29
JP2013249313A (en) 2013-12-12
EP2491943A3 (en) 2013-01-23
EP3305313A1 (en) 2018-04-11
JP2011026346A (en) 2011-02-10
EP3479838A1 (en) 2019-05-08
CN102784383B (en) 2014-09-17
EP1599216A4 (en) 2009-11-11
AU2004209663A1 (en) 2004-08-19
EP1599216A2 (en) 2005-11-30
HK1178794A1 (en) 2013-09-19
ES2436011T3 (en) 2013-12-26
EP3842055A1 (en) 2021-06-30
PT2656854E (en) 2015-09-03
JP2015180693A (en) 2015-10-15
CY1116575T1 (en) 2017-03-15
EP2491943B1 (en) 2018-10-10
EP3659618A1 (en) 2020-06-03
EP2865385B1 (en) 2016-11-16
CN104225574B (en) 2017-01-11
JP5837542B2 (en) 2015-12-24
CN102784383A (en) 2012-11-21
US20230293624A1 (en) 2023-09-21
US20120021970A1 (en) 2012-01-26
CY1114959T1 (en) 2016-12-14
EP2491943A2 (en) 2012-08-29
HK1131995A1 (en) 2010-02-12
US7576061B2 (en) 2009-08-18
WO2004070054A2 (en) 2004-08-19
AU2004209663A2 (en) 2004-08-19
SI2656854T1 (en) 2015-09-30
ES2540897T3 (en) 2015-07-14
EP1599216B9 (en) 2015-02-11
US7718620B2 (en) 2010-05-18
EP1599216B1 (en) 2013-11-06
JP6166312B2 (en) 2017-07-19
JP2019089773A (en) 2019-06-13
US20150359838A1 (en) 2015-12-17
US20040248808A1 (en) 2004-12-09
JP2006516652A (en) 2006-07-06
US20130244957A1 (en) 2013-09-19
CA2515080C (en) 2012-04-10
US20200038472A1 (en) 2020-02-06
JP6126059B2 (en) 2017-05-10
DK2865385T3 (en) 2016-12-19
US20070027087A1 (en) 2007-02-01
HK1190930A1 (en) 2014-07-18
EP3144009A1 (en) 2017-03-22
PT1599216E (en) 2013-12-17
CN104225574A (en) 2014-12-24
JP2015007127A (en) 2015-01-15
US8957030B2 (en) 2015-02-17
ES2605504T3 (en) 2017-03-14
EP2656854B1 (en) 2015-05-20
DK1599216T3 (en) 2013-12-09
JP4838114B2 (en) 2011-12-14
JP5775285B2 (en) 2015-09-09
HK1090571A1 (en) 2006-12-29
EP2865385A1 (en) 2015-04-29
EP2656854A1 (en) 2013-10-30

Similar Documents

Publication Publication Date Title
CA2515080A1 (en) Methods for preventing mitochondrial permeability transition
JP2006516652A5 (en)
RU2006130431A (en) METHOD FOR REDUCING OXIDATIVE DAMAGE (OPTIONS)
JP2007518818A5 (en)
Schiller et al. Synthesis and in vitro opioid activity profiles of DALDA analogues
US6320024B1 (en) Method for design of substances that enhance memory and improve the quality of life
Coy et al. Synthesis and opioid activities of stereoisomers and other D-amino acid analogs of methionine-enkephalin
US3832337A (en) Peptide enzyme inhibitors
US6245738B1 (en) Cytokine restraining agents
CA2370289A1 (en) Neuronal exocytosis inhibiting peptides and cosmetic and pharmaceutical compositions containing said peptides
Okada et al. Structural studies of [2′, 6′-dimethyl-L-tyrosine1] endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond
AU681372B2 (en) New peptides
CN113402586A (en) Polypeptide and application thereof
US9611297B1 (en) Compositions and methods for the treatment of cast nephropathy and related conditions
CA1249698A (en) Retro-inverso analogues of c-terminal penta and hexapeptides of substance p
HUE031856T2 (en) Stabilized melanocortin ligands
US5840697A (en) Peptide inhibitors of calmodulin
Chao et al. Preparation and use of the 4-[1-[N-(9-fluorenylmethyloxycarbonyl) amino]-2-(trimethylsilyl) ethyl] phenoxyacetic acid linkage agent for solid-phase synthesis of C-terminal peptide amides: improved yields of tryptophan-containing peptides
Sasaki et al. On the degradation of dermorphin and D-Arg2-dermorphin analogs by a soluble rat brain extract
Misicka et al. Synthesis and biological properties of gamma-glutamyl-dermorphin, a prodrug
NO952635L (en) Synthetic peptide derivatives and salts thereof
NO300978B1 (en) Analogous Process for Preparation of Pharmaceutically Active Peptide
US3268502A (en) Undecapeptides
US5891848A (en) Peptide fragments
WO1995035316A1 (en) New opioid peptide antagonists

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20240205