WO1999050658A3 - Methods and compounds for modulating nuclear receptor activity - Google Patents

Methods and compounds for modulating nuclear receptor activity Download PDF

Info

Publication number
WO1999050658A3
WO1999050658A3 PCT/US1999/006937 US9906937W WO9950658A3 WO 1999050658 A3 WO1999050658 A3 WO 1999050658A3 US 9906937 W US9906937 W US 9906937W WO 9950658 A3 WO9950658 A3 WO 9950658A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
compounds
nuclear receptor
ligand binding
receptor activity
Prior art date
Application number
PCT/US1999/006937
Other languages
French (fr)
Other versions
WO1999050658A2 (en
Inventor
Andrew Shiau
Peter J Kushner
David A Agard
Geoffrey L Greene
Original Assignee
Univ California
Arch Dev Corp
Andrew Shiau
Peter J Kushner
David A Agard
Geoffrey L Greene
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 Univ California, Arch Dev Corp, Andrew Shiau, Peter J Kushner, David A Agard, Geoffrey L Greene filed Critical Univ California
Priority to CA002324060A priority Critical patent/CA2324060A1/en
Priority to EP99916206A priority patent/EP1144997A3/en
Priority to KR1020007010940A priority patent/KR20010042373A/en
Priority to AU34571/99A priority patent/AU3457199A/en
Priority to JP2000541516A priority patent/JP2002516983A/en
Publication of WO1999050658A2 publication Critical patent/WO1999050658A2/en
Publication of WO1999050658A3 publication Critical patent/WO1999050658A3/en

Links

Classifications

    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6875—Nucleoproteins
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • 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
    • A61P9/06—Antiarrhythmics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
    • C07K14/721—Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor
    • 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
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
    • G01N2333/723—Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/20—Screening for compounds of potential therapeutic value cell-free systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Hematology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Endocrinology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Obesity (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Reproductive Health (AREA)
  • Child & Adolescent Psychology (AREA)
  • Zoology (AREA)
  • Heart & Thoracic Surgery (AREA)

Abstract

The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor activity, and nuclear receptor ligand binding. The invention includes a method for identifying residues comprising a ligand binding domain for a nuclear receptor of interest. Also included in a method of identifying agonists and/or antagonists that bind to the ligand binding domain of the nuclear receptors, and the estrogen receptor in particular. The invention is exemplified by identification and manipulation of the ligand binding domain of the estrogen receptor and compounds that bind to this site. The methods can be applied to other nuclear receptors including TR, GR and PR.
PCT/US1999/006937 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity WO1999050658A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA002324060A CA2324060A1 (en) 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity
EP99916206A EP1144997A3 (en) 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity
KR1020007010940A KR20010042373A (en) 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity
AU34571/99A AU3457199A (en) 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity
JP2000541516A JP2002516983A (en) 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US7995698P 1998-03-30 1998-03-30
US60/079,956 1998-03-30
US11314698P 1998-12-16 1998-12-16
US11301498P 1998-12-16 1998-12-16
US60/113,014 1998-12-16
US60/113,146 1998-12-16

Publications (2)

Publication Number Publication Date
WO1999050658A2 WO1999050658A2 (en) 1999-10-07
WO1999050658A3 true WO1999050658A3 (en) 2001-08-16

Family

ID=27373576

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/006937 WO1999050658A2 (en) 1998-03-30 1999-03-30 Methods and compounds for modulating nuclear receptor activity

Country Status (6)

Country Link
EP (1) EP1144997A3 (en)
JP (1) JP2002516983A (en)
KR (1) KR20010042373A (en)
AU (1) AU3457199A (en)
CA (1) CA2324060A1 (en)
WO (1) WO1999050658A2 (en)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003523498A (en) * 1998-03-30 2003-08-05 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Methods and compounds for modulating the binding of nuclear receptor co-activator
AU2818200A (en) * 1999-03-01 2000-09-21 Karo Bio Ab Homology models of the glucocorticoid receptor
AU775928B2 (en) 1999-10-14 2004-08-19 Bristol-Myers Squibb Company Crystallographic structure of the androgen receptor ligand binding domain
FR2801311B1 (en) 1999-11-22 2005-08-26 Centre Nat Rech Scient POLYPEPTIDES DERIVED FROM THE NUCLEAR RECEPTOR OF VITAMIN D, AND USES THEREOF IN PARTICULAR IN THE SCREENING OF ANALOGUES OF VITAMIN D
CA2415103A1 (en) * 2000-06-30 2002-01-10 The Regents Of The University Of California Methods and compounds for modulating nuclear receptor coactivator binding
DE10036461A1 (en) * 2000-07-25 2002-02-07 Bayer Ag Ligand binding domain of the Ultraspiracle (USP) protein
JP4593754B2 (en) * 2000-10-13 2010-12-08 一般財団法人 化学物質評価研究機構 Method for determining 50% inhibitory concentration of chemical substances
JP2002296282A (en) * 2001-04-02 2002-10-09 Enbiotec Laboratories:Kk Method of detecting exogeneous endocrine disturbing substance
WO2003004458A1 (en) * 2001-07-03 2003-01-16 Biovitrum Ab New compounds
GB0209507D0 (en) * 2002-04-25 2002-06-05 Karobio Ab Nuclear receptor structure
US7302347B2 (en) * 2002-12-10 2007-11-27 The Regents Of The University Of California Method for creating specific, high affinity nuclear receptor pharmaceuticals
WO2005022436A1 (en) * 2003-08-29 2005-03-10 National Institute Of Advanced Industrial Science And Technology Protein structure three-dimensional display system for indication of protein function manifestation mechanism
US7264813B2 (en) 2003-09-24 2007-09-04 Nikken Sohonsha Corporation Therapeutic uses of Dunaliella powder
US20070087346A1 (en) * 2003-10-24 2007-04-19 Gennaro Ciliberto Orthogonal gene switches
CN105362151A (en) * 2010-03-31 2016-03-02 株式会社爱茉莉太平洋 Cosmetic composition comprising coumestrol or a bean extract containing coumestrol for skin care
EP3205648A1 (en) 2010-06-10 2017-08-16 Seragon Pharmaceuticals, Inc. Estrogen receptor modulators and uses thereof
EA029559B1 (en) 2011-12-14 2018-04-30 Серагон Фармасьютикалс, Инк. Fluorinated estrogen receptor modulators and use thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992000091A1 (en) * 1990-07-02 1992-01-09 Bioligand, Inc. Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof
WO1993006121A1 (en) * 1991-09-18 1993-04-01 Affymax Technologies N.V. Method of synthesizing diverse collections of oligomers
WO1994028028A1 (en) * 1993-05-27 1994-12-08 Selectide Corporation Topologically segregated, encoded solid phase libraries
EP0639584A1 (en) * 1993-06-22 1995-02-22 Interpharm Laboratories Ltd. Preparation and screening of highly diverse peptide libraries for binding activity
WO1997021993A2 (en) * 1995-12-13 1997-06-19 The Regents Of The University Of California Nuclear receptor ligands and ligand binding domains

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992000091A1 (en) * 1990-07-02 1992-01-09 Bioligand, Inc. Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof
WO1993006121A1 (en) * 1991-09-18 1993-04-01 Affymax Technologies N.V. Method of synthesizing diverse collections of oligomers
WO1994028028A1 (en) * 1993-05-27 1994-12-08 Selectide Corporation Topologically segregated, encoded solid phase libraries
EP0639584A1 (en) * 1993-06-22 1995-02-22 Interpharm Laboratories Ltd. Preparation and screening of highly diverse peptide libraries for binding activity
WO1997021993A2 (en) * 1995-12-13 1997-06-19 The Regents Of The University Of California Nuclear receptor ligands and ligand binding domains

Also Published As

Publication number Publication date
CA2324060A1 (en) 1999-10-07
WO1999050658A2 (en) 1999-10-07
KR20010042373A (en) 2001-05-25
EP1144997A3 (en) 2002-08-28
EP1144997A2 (en) 2001-10-17
JP2002516983A (en) 2002-06-11
AU3457199A (en) 1999-10-18

Similar Documents

Publication Publication Date Title
WO1999050658A3 (en) Methods and compounds for modulating nuclear receptor activity
WO1999060014A3 (en) Methods and compounds for modulating nuclear receptor coactivator binding
WO2001016133A3 (en) 8-substituted-6-trifluoromethyl-9-pyrido[3,2-g]quinoline compounds as androgen receptor modulators
ZA200007630B (en) Bitumen emulsions, method for obtaining them and compositions containing same.
ZA995907B (en) Automated in situ testing of railroad telemetry radios.
WO1997021993A3 (en) Nuclear receptor ligands and ligand binding domains
AU4552099A (en) Multivalent agonists, partial agonists, inverse agonists and antagonists of the 5HT2 receptors
DE69802790T2 (en) CEMENT COMPOSITIONS AND METHOD FOR USE IN UNDERGROUND DRILL HOLES
AU4345900A (en) Interface for an enterprise resource planning program
ATE416173T1 (en) 1-(3-HETEROARYLPROPYL- OR -PROP-2-ENYL)-4- BENZYLPIPERIDINE AS NMDA RECEPTOR ANTAGONISTS
DE69904013T2 (en) METHOD AND DEVICE FOR CRUSHING WASTE, EVEN FOR WASTE NOT PROVIDED FOR IT
AU2023499A (en) Pth receptor and screening assay utilizing the same
DE69826527D1 (en) DEVICE FOR COMPLETING AN UNDERGROUND BORE AND METHOD FOR THE USE THEREOF
WO2002056016A3 (en) Method for identifying a ligand for a biological substrate
WO2001085930A3 (en) Methods and compounds for modulating melanocortin receptor ligand binding and activity
DE69907716D1 (en) DEVICE AND METHOD FOR EXAMINING SOLID PROPERTIES BY INVERSE CHROMATOGRAPHY
WO2004046323A3 (en) Structure of the farnesoid x receptor ligand binding domain and methods of use therefor
MY142857A (en) Treatment of incontinence with 5-ht2c receptor agonists
WO2002002488A3 (en) Methods and compounds for modulating nuclear receptor coactivator binding
SG11201909281QA (en) Apparatus and method for the non-destructive measurement of hydrogen diffusivity
WO2002097450A3 (en) Nuclear magnetic resonance-docking of compounds
AU7485996A (en) Neuropeptide y-y5 receptor
EP1752544A4 (en) Probe for detecting nuclear receptor agonist or antagonist and method of screening agonist or antagonist to nuclear receptor with the use of the same
SG11201909860RA (en) Apparatus and method for the non-destructive measurement of hydrogen diffusivity
AU5924699A (en) Methods for identifying hot-spot residues of binding proteins and small compounds that bind to the same

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AU CA JP KR US

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 34571/99

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 2324060

Country of ref document: CA

Ref country code: CA

Ref document number: 2324060

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1020007010940

Country of ref document: KR

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 541516

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1999916206

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1020007010940

Country of ref document: KR

AK Designated states

Kind code of ref document: A3

Designated state(s): AU CA JP KR US

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

WWP Wipo information: published in national office

Ref document number: 1999916206

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 09830693

Country of ref document: US

WWR Wipo information: refused in national office

Ref document number: 1020007010940

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1999916206

Country of ref document: EP