MX2010009673A - Modulation of enzymatic structure, activity, and/or expression level. - Google Patents

Modulation of enzymatic structure, activity, and/or expression level.

Info

Publication number
MX2010009673A
MX2010009673A MX2010009673A MX2010009673A MX2010009673A MX 2010009673 A MX2010009673 A MX 2010009673A MX 2010009673 A MX2010009673 A MX 2010009673A MX 2010009673 A MX2010009673 A MX 2010009673A MX 2010009673 A MX2010009673 A MX 2010009673A
Authority
MX
Mexico
Prior art keywords
activity
complex
modulator
expression level
subunit
Prior art date
Application number
MX2010009673A
Other languages
Spanish (es)
Inventor
Bhasin Rajinder
Bingham Paul
Boteju Lakmal
Zachar Zuzana
Original Assignee
Robert Shorr
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 Robert Shorr filed Critical Robert Shorr
Publication of MX2010009673A publication Critical patent/MX2010009673A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/20—Esters of monothiocarboxylic acids
    • C07C327/32—Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

A pharmaceutically-acceptable modulator of the structure, activity, or expression level of an enzyme complex, such as the pyruvate dehydrogenase (PD) complex, in the mitochondria of warm-blooded animals, including humans, and methods of use thereof, comprises an effective amount of at least one lipoic acid derivative and at least one pharmaceutically-acceptable carrier thereof. By preventing the detoxification of toxic metabolites of anaerobic glycolysis through inhibition of the activity of the PD complex Elα subunit, the modulator increases PD kinase activity and concomitantly decreases PD phosphatase activity, obliging increased oxidative phosphorylation activity in the mitochondrion. As a cell characterized by hyperprolif eration, such as a tumor cell, cannot also generate acetyl-CoA and NADH because of the action of the modulator in inhibiting the action of the E2 subunit of the PD complex, the mitochondrial membrane polarization is lost, facilitating cell death.
MX2010009673A 2008-03-04 2008-03-04 Modulation of enzymatic structure, activity, and/or expression level. MX2010009673A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2008/002853 WO2009110859A1 (en) 2008-03-04 2008-03-04 Modulation of enzymatic structure, activity, and/or expression level

Publications (1)

Publication Number Publication Date
MX2010009673A true MX2010009673A (en) 2011-03-15

Family

ID=41056265

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2010009673A MX2010009673A (en) 2008-03-04 2008-03-04 Modulation of enzymatic structure, activity, and/or expression level.

Country Status (10)

Country Link
EP (1) EP2260019A4 (en)
JP (1) JP2011513395A (en)
KR (1) KR20110004846A (en)
CN (1) CN102089276A (en)
AU (1) AU2008352076A1 (en)
BR (1) BRPI0821176A2 (en)
CA (1) CA2717511A1 (en)
IL (1) IL207943A0 (en)
MX (1) MX2010009673A (en)
WO (1) WO2009110859A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8263653B2 (en) * 2007-04-18 2012-09-11 Cornerstone Pharmaceuticals, Inc. Pharmaceutical formulations containing lipoic acid derivatives
WO2009123597A1 (en) * 2008-04-04 2009-10-08 Robert Shorr Pharmaceutical composition
AU2014398233B2 (en) 2014-06-19 2019-11-28 Rafael Pharmaceuticals, Inc. Pharmaceutical compounds
ES2819175T3 (en) 2014-06-19 2021-04-15 Rafael Pharmaceuticals Inc Pharmaceutical compounds
TW202038930A (en) * 2018-12-20 2020-11-01 美商拉斐爾製藥公司 Oral therapy using 6,8-bis-benzylthio-octanoic acid

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5463093A (en) * 1993-11-26 1995-10-31 Garnett; Merrill Palladium complexes and methods for using same in the treatment of tumors or Psoriasis
DE4343593C2 (en) * 1993-12-21 1998-05-20 Asta Medica Ag Use of R - (+) - alpha-lipoic acid, R - (-) - dihydrolipoic acid or the metabolites as well as their salts, esters, amides for the treatment of compensated and decompensated insulin resistance
MXPA01004152A (en) * 1998-10-26 2002-06-04 Univ New York State Res Found Lipoic acid derivatives and their use in treatment of disease.
US6284786B1 (en) * 1999-02-16 2001-09-04 The Center For The Improvement Of Human Functioning, Int'l., Inc. Treatment of cancer using lipoic acid in combination with ascorbic acid
IT1312060B1 (en) * 1999-04-09 2002-04-04 Antibioticos Spa USE OF ALPHA LIPOIC ACID IN ANTIMETASTATIC TREATMENT.
EP1172110A3 (en) * 2000-07-07 2003-09-17 Basf Aktiengesellschaft Use of lipoic acid as a bioavailaty enhancer of mineral salts
US20020071234A1 (en) * 2000-10-25 2002-06-13 George Alexanian Battery powered programmable remote switch controller
WO2006119355A2 (en) * 2005-05-03 2006-11-09 Albert Einstein College Of Medicine Of Yeshiva University Mammalian hypothalamic nutrient modulation of glucose metabolism
AU2008242827B2 (en) * 2007-04-18 2014-06-05 Cornerstone Pharmaceuticals, Inc. Pharmaceutical formulations containing lipoic acid derivatives
KR101644192B1 (en) * 2007-04-18 2016-07-29 코너스톤 파마슈티칼스, 인크. Lipoic acid derivatives

Also Published As

Publication number Publication date
AU2008352076A1 (en) 2009-09-11
EP2260019A1 (en) 2010-12-15
CN102089276A (en) 2011-06-08
CA2717511A1 (en) 2009-09-11
IL207943A0 (en) 2010-12-30
JP2011513395A (en) 2011-04-28
EP2260019A4 (en) 2011-08-03
KR20110004846A (en) 2011-01-14
WO2009110859A1 (en) 2009-09-11
BRPI0821176A2 (en) 2015-10-06

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