WO2012021291A2 - Methods of treating obstructive lung diseases using bitter tastants - Google Patents

Methods of treating obstructive lung diseases using bitter tastants Download PDF

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Publication number
WO2012021291A2
WO2012021291A2 PCT/US2011/045537 US2011045537W WO2012021291A2 WO 2012021291 A2 WO2012021291 A2 WO 2012021291A2 US 2011045537 W US2011045537 W US 2011045537W WO 2012021291 A2 WO2012021291 A2 WO 2012021291A2
Authority
WO
WIPO (PCT)
Prior art keywords
subject
bitter
smooth muscle
bitter taste
airway
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.)
Ceased
Application number
PCT/US2011/045537
Other languages
English (en)
French (fr)
Other versions
WO2012021291A3 (en
Inventor
Stephen B. Liggett
Wayne C. H. Wang
Deepak A. Deshpande
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.)
University of Maryland, Baltimore
University of Maryland, College Park
Original Assignee
University of Maryland, Baltimore
University of Maryland, College Park
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 University of Maryland, Baltimore, University of Maryland, College Park filed Critical University of Maryland, Baltimore
Priority to EP11816786.5A priority Critical patent/EP2603213A4/en
Priority to JP2013524091A priority patent/JP2013533310A/ja
Priority to US13/812,508 priority patent/US9579315B2/en
Publication of WO2012021291A2 publication Critical patent/WO2012021291A2/en
Publication of WO2012021291A3 publication Critical patent/WO2012021291A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • 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
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/49—Cinchonan derivatives, e.g. quinine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5061—Muscle cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/12—Pulmonary diseases
    • G01N2800/122—Chronic or obstructive airway disorders, e.g. asthma COPD

Definitions

  • GPCRs G-protein coupled receptors
  • GPCRs G-protein coupled receptors
  • the present invention provides methods of relaxing airway smooth muscle (ASM) in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a bitter tastant to a subject in need of ASM relaxation.
  • ASM airway smooth muscle
  • the present invention provides methods of treating or preventing bronchoconstriction or bronchospasm in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a bitter tastant to a subject in need of treatment or prevention of bronchoconstriction or bronchospasm.
  • the subject receiving treatment is a human or non-human animal, e.g., a non-human primate, bird, horse, cow, goat, sheep, a companion animal, such as a dog, cat or rodent, or other mammal.
  • the subject is a human.
  • the ameliorating, blocking, reducing, decreasing or inhibiting is about 100%, 99%, 98%, 97%, 96%, 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5% or 1% versus a subject to which a pharmaceutical composition has not been administered.
  • Bitter tastant receptors to which a test compound can bind include, for example, T2R10; T2R14; T2R44; T2R5; T2R4; T2R48; T2R3; T2R49; T2R45; T2R50; T2R47; T2R9; T2R13; TAS2R55; TAS2R46; TAS2R1; TAS2R8 (nomenclature as in Table 2; see Table 3 for alternative nomenclature).
  • the bitter tastant can bind to one or more of the aforementioned bitter tastant receptors.
  • Also provided herein are methods for identifying compounds that are bitter taste receptor agonists.
  • bitter taste receptor antagonists are performed by treating the cells with the proposed antagonist and a known agonist for a bitter taste receptor. Comparison of the [Ca 2+ ]; signal from the known agonist and the signal from that agonist in the presence of the proposed antagonist compound provides evidence that the test compound is acting to block access of the agonist to the receptor, which is indicative of an antagonist. The use of various doses of the proposed antagonist reveals the potency (defined above) and the efficacy (here defined as the maximal inhibition of the agonist signal).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Toxicology (AREA)
  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US2011/045537 2010-08-09 2011-07-27 Methods of treating obstructive lung diseases using bitter tastants Ceased WO2012021291A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP11816786.5A EP2603213A4 (en) 2010-08-09 2011-07-27 METHOD FOR THE TREATMENT OF OBSTRUCTIVE LUNG DISEASES USING BITTER TASTES
JP2013524091A JP2013533310A (ja) 2010-08-09 2011-07-27 苦味物質を使用して閉塞性肺疾患を処置する方法
US13/812,508 US9579315B2 (en) 2010-08-09 2011-07-27 Methods of treating obstructive lung diseases using bitter tastants

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US37194610P 2010-08-09 2010-08-09
US61/371,946 2010-08-09
US40588310P 2010-10-22 2010-10-22
US61/405,883 2010-10-22

Publications (2)

Publication Number Publication Date
WO2012021291A2 true WO2012021291A2 (en) 2012-02-16
WO2012021291A3 WO2012021291A3 (en) 2012-05-18

Family

ID=45568120

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/045537 Ceased WO2012021291A2 (en) 2010-08-09 2011-07-27 Methods of treating obstructive lung diseases using bitter tastants

Country Status (4)

Country Link
US (1) US9579315B2 (enExample)
EP (1) EP2603213A4 (enExample)
JP (1) JP2013533310A (enExample)
WO (1) WO2012021291A2 (enExample)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014022139A1 (en) * 2012-07-31 2014-02-06 University Of Massachusetts Medical School Methods for identifying agents for treating smooth muscle disorders and compositions thereof
EP2865421A1 (en) * 2013-10-28 2015-04-29 Albert-Ludwigs-Universität Freiburg Bitter taste receptor agonists for topical use
US9918961B2 (en) 2014-02-19 2018-03-20 Kind Consumer Limited Cannabinoid inhaler and composition therefor
US10413521B2 (en) 2014-02-14 2019-09-17 Kind Consumer Limited Cannabinoid compositions and uses
US20210161838A1 (en) * 2018-07-02 2021-06-03 Aardvark Therapeutics Inc. Oral Pharmaceutical Formulations of Bitter Compounds for Asthma

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2742350B1 (en) * 2011-08-08 2019-10-30 The Coca-Cola Company Cell lines comprising endogenous taste receptors and their uses
WO2013112865A1 (en) * 2012-01-27 2013-08-01 The Trustees Of The University Of Pennsylvania Diagnosis and treatment for respiratory tract diseases
US12268660B2 (en) 2018-07-11 2025-04-08 Aardvark Therapeutics Inc. Oral pharmaceutical formulations of bitter compounds for pulmonary hypertension
KR102140493B1 (ko) * 2019-05-30 2020-08-03 충북대학교 산학협력단 데나토늄을 유효성분으로 포함하는 골 질환의 예방 또는 치료용 조성물
WO2021211923A1 (en) * 2020-04-16 2021-10-21 Pulmoquine Therapeutics, Inc. Compositions and methods for treating disease
US12257248B2 (en) * 2020-09-01 2025-03-25 University Of South Florida Bronchodilators for treating obstructive lung disease
CN113694053A (zh) * 2021-09-29 2021-11-26 常州大学 氟芬那酸作为有效成分在制备气道平滑肌舒张剂中的应用

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CA2372443C (en) * 1999-04-30 2010-07-13 Apt Pharmaceuticals, L.L.C. Local administration of anti-malarial agents for the treatment of inflammatory diseases
US7364867B2 (en) * 2000-04-17 2008-04-29 The Mount Sinai School Of Medicine Method of identifying bitter compounds by employing TRP8, a transient receptor potential channel expressed in taste receptor cells
US7368285B2 (en) 2001-03-07 2008-05-06 Senomyx, Inc. Heteromeric umami T1R1/T1R3 taste receptors and isolated cells that express same
US7794959B2 (en) * 2001-04-05 2010-09-14 Senomyx, Inc. Identification of bitter receptors for hydrolyzed soy protein
US7883856B2 (en) * 2001-04-05 2011-02-08 Senomyx Inc. Identification of bitter ligands that specifically activate human T2R receptors and related assays for identifying human bitter taste modulators
US20040208833A1 (en) * 2003-02-04 2004-10-21 Elan Pharma International Ltd. Novel fluticasone formulations
US7339051B2 (en) * 2003-04-28 2008-03-04 Isis Pharmaceuticals, Inc. Compositions and methods for the treatment of severe acute respiratory syndrome (SARS)
EP1851548A4 (en) * 2005-02-08 2010-04-28 Senomyx Inc HUMAN T2R RECEPTORS FOR ACETAMINOPHES, RANITIDINE, STRYCHNIN AND DENATONIUM, AND ASSOCIATED ASSAYS FOR IDENTIFYING MODULATORS BITTER TASTE
EP2353590A1 (en) * 2005-02-15 2011-08-10 Elan Pharma International Limited Aerosol and injectable formulations of nanoparticulate benzodiazepine
AU2006299383A1 (en) * 2005-10-04 2007-04-12 Nitromed, Inc. Methods for treating respiratory disorders
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014022139A1 (en) * 2012-07-31 2014-02-06 University Of Massachusetts Medical School Methods for identifying agents for treating smooth muscle disorders and compositions thereof
EP2865421A1 (en) * 2013-10-28 2015-04-29 Albert-Ludwigs-Universität Freiburg Bitter taste receptor agonists for topical use
US10413521B2 (en) 2014-02-14 2019-09-17 Kind Consumer Limited Cannabinoid compositions and uses
US10561634B2 (en) 2014-02-14 2020-02-18 Kind Consumer Limited Cannabinoid compositions and uses
US9918961B2 (en) 2014-02-19 2018-03-20 Kind Consumer Limited Cannabinoid inhaler and composition therefor
US20210161838A1 (en) * 2018-07-02 2021-06-03 Aardvark Therapeutics Inc. Oral Pharmaceutical Formulations of Bitter Compounds for Asthma
US12201593B2 (en) * 2018-07-02 2025-01-21 Aardvark Therapeutics Inc. Oral pharmaceutical formulations of bitter compounds for asthma

Also Published As

Publication number Publication date
JP2013533310A (ja) 2013-08-22
US20130131108A1 (en) 2013-05-23
EP2603213A4 (en) 2014-02-19
EP2603213A2 (en) 2013-06-19
US9579315B2 (en) 2017-02-28
WO2012021291A3 (en) 2012-05-18

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