WO2012051306A3 - Compositions and methods for modulating mitochondrial proteases - Google Patents

Compositions and methods for modulating mitochondrial proteases Download PDF

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Publication number
WO2012051306A3
WO2012051306A3 PCT/US2011/055974 US2011055974W WO2012051306A3 WO 2012051306 A3 WO2012051306 A3 WO 2012051306A3 US 2011055974 W US2011055974 W US 2011055974W WO 2012051306 A3 WO2012051306 A3 WO 2012051306A3
Authority
WO
WIPO (PCT)
Prior art keywords
tfam
compositions
increased
methods
life
Prior art date
Application number
PCT/US2011/055974
Other languages
French (fr)
Other versions
WO2012051306A2 (en
Inventor
Shaharyar Khan
Original Assignee
Gencia Corporation
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 Gencia Corporation filed Critical Gencia Corporation
Publication of WO2012051306A2 publication Critical patent/WO2012051306A2/en
Publication of WO2012051306A3 publication Critical patent/WO2012051306A3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compositions and methods for modulating oxidative phosphorylation in a subject are provided. The compositions include an effective amount of mitochondrial protease inhibitor conjugated to a mitochondrial targeting moiety to inhibit or reduce proteolysis of TFAM. In a preferred embodiment, the protease inhibitor inhibits Lon protease activity on TFAM resulting in increased TFAM levels and/or increased TFAM half-life. Increases in TFAM concentration or increased TFAM half-life stimulate oxidative metabolism causing an increase in oxidative phosphorylation. A preferred mitochondrial targeting moiety is a liphophilic cation such as triphenyl phosphonium.
PCT/US2011/055974 2010-10-12 2011-10-12 Compositions and methods for modulating mitochondrial proteases WO2012051306A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39238010P 2010-10-12 2010-10-12
US61/392,380 2010-10-12

Publications (2)

Publication Number Publication Date
WO2012051306A2 WO2012051306A2 (en) 2012-04-19
WO2012051306A3 true WO2012051306A3 (en) 2012-07-05

Family

ID=44993165

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/055974 WO2012051306A2 (en) 2010-10-12 2011-10-12 Compositions and methods for modulating mitochondrial proteases

Country Status (1)

Country Link
WO (1) WO2012051306A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ2013308A3 (en) * 2013-04-24 2014-07-02 Smart Brain s.r.o. Tamoxifen derivatives exhibiting activity against tumors, especially tumors with higher protein level HER2
WO2015002996A1 (en) * 2013-07-01 2015-01-08 University Of Georgia Research Foundation, Inc. Precise delivery of therapeutic agents to cell mitochondria for anti-cancer therapy
US20220340908A1 (en) * 2019-09-25 2022-10-27 University Of Massachusetts Methods for depletion of deleterious mitochondrial genomes
TW202342061A (en) * 2021-12-06 2023-11-01 美商普萊萃歐治療公司 Lonp1 inhibitors, uses and methods

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009018112A2 (en) * 2007-07-27 2009-02-05 Invitrogen Corporation The use of novel coumarins as glutathione and thiol labels

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ207394A (en) 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
US6156337A (en) 1994-07-08 2000-12-05 Opperbas Holding B.V. Method for high loading of vesicles with biopolymeric substances
US20030069208A1 (en) 1997-11-25 2003-04-10 University Of Otago Mitochondrially targeted antioxidants
ES2411962T3 (en) 2003-10-24 2013-07-09 Gencia Corporation Methods and compositions for delivering polynucleotides
WO2006094203A1 (en) 2005-03-02 2006-09-08 Northeastern University Mitochondriotropic phospholipid vesicles
WO2007112107A2 (en) 2006-03-24 2007-10-04 Gencia Corporation Synthetic lipid rafts and methods of use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009018112A2 (en) * 2007-07-27 2009-02-05 Invitrogen Corporation The use of novel coumarins as glutathione and thiol labels

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BAYOT ET AL: "Towards the control of intracellular protein turnover: Mitochondrial Lon protease inhibitors versus proteasome inhibitors", BIOCHIMIE, MASSON, PARIS, FR, vol. 90, no. 2, 25 October 2007 (2007-10-25), pages 260 - 269, XP022438300, ISSN: 0300-9084, DOI: 10.1016/J.BIOCHI.2007.10.010 *
HORTON K L ET AL: "Mitochondria-Penetrating Peptides", CHEMISTRY AND BIOLOGY, CURRENT BIOLOGY, LONDON, GB, vol. 15, no. 4, 21 April 2008 (2008-04-21), pages 375 - 382, XP022613220, ISSN: 1074-5521, [retrieved on 20080415], DOI: 10.1016/J.CHEMBIOL.2008.03.015 *

Also Published As

Publication number Publication date
WO2012051306A2 (en) 2012-04-19

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