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WO2000076529A3 - Use of estrogen receptor agonists or antagonists for treating growth, bone disorders - Google Patents

Use of estrogen receptor agonists or antagonists for treating growth, bone disorders Download PDF

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Publication number
WO2000076529A3
WO2000076529A3 PCT/GB2000/002283 GB0002283W WO0076529A3 WO 2000076529 A3 WO2000076529 A3 WO 2000076529A3 GB 0002283 W GB0002283 W GB 0002283W WO 0076529 A3 WO0076529 A3 WO 0076529A3
Authority
WO
WIPO (PCT)
Prior art keywords
erko
derko
estrogen
skeleton
berko
Prior art date
Application number
PCT/GB2000/002283
Other languages
French (fr)
Other versions
WO2000076529A2 (en
Inventor
Claes Ohlsson
Jan Ake Gustafsson
Original Assignee
Karobio Ab
Dean John Paul
Claes Ohlsson
Jan Ake Gustafsson
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 Karobio Ab, Dean John Paul, Claes Ohlsson, Jan Ake Gustafsson filed Critical Karobio Ab
Priority to AU55454/00A priority Critical patent/AU5545400A/en
Priority to EP00940530A priority patent/EP1185287A2/en
Priority to CA002376441A priority patent/CA2376441A1/en
Publication of WO2000076529A2 publication Critical patent/WO2000076529A2/en
Publication of WO2000076529A3 publication Critical patent/WO2000076529A3/en

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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
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Androgens regulate the male skeleton directly via a stimulation of androgen receptors and indirectly via aromatization of androgens into estrogen and thereafter stimulation of estrogen receptors (ER). In order to investigate the relative importance of estrogen receptor subtypes in the regulation of the male skeleton, the skeletal phenotypes of wild type (WT), ERα, Knockout (ERKO), ERβ Knockout (BERKO) and ERα/β Double Knockout (DERKO) mice were compared. ERKO and DERKO had reduced body weight as well as longitudinal bone growth. Furthermore, ERKO and DERKO but not BERKO demonstrated a pronounced decrease in bone mineral content in the long bones and in the axial skeleton. This decrease in BMC was due to cortical ostopenia as a result of decreased radial growth of the bones. Mechanical testing demonstrated that femora from ERKO were weaker as a result of the altered cortical bone dimensions. No significant change in trabecular BMD was seen in any group. ERKO demonstrated decreased serum levels of osteocalcin and IGF-I. Furthermore, serum levels of IGF-I were correlated to most of the skeletal changes seen in DERKO and ERKO. In conclusion , the skeletal phenotypes of DERKO and ERKO are similar and clearly distinguishable from WT and BERKO. Therefore, ERα, but not ERβ, mediates the effect of estrogen in the skeleton of male mice.
PCT/GB2000/002283 1999-06-11 2000-06-12 Use of estrogen receptor agonists or antagonists for treating growth, bone disorders WO2000076529A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU55454/00A AU5545400A (en) 1999-06-11 2000-06-12 Estrogen receptor
EP00940530A EP1185287A2 (en) 1999-06-11 2000-06-12 Use of estrogen receptor agonists or antagonists for treating growth, bone disorders
CA002376441A CA2376441A1 (en) 1999-06-11 2000-06-12 Estrogen receptor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9913649.1 1999-06-11
GBGB9913649.1A GB9913649D0 (en) 1999-06-11 1999-06-11 Estrogen receptor

Publications (2)

Publication Number Publication Date
WO2000076529A2 WO2000076529A2 (en) 2000-12-21
WO2000076529A3 true WO2000076529A3 (en) 2001-07-12

Family

ID=10855195

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/002283 WO2000076529A2 (en) 1999-06-11 2000-06-12 Use of estrogen receptor agonists or antagonists for treating growth, bone disorders

Country Status (5)

Country Link
EP (1) EP1185287A2 (en)
AU (1) AU5545400A (en)
CA (1) CA2376441A1 (en)
GB (1) GB9913649D0 (en)
WO (1) WO2000076529A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA83620C2 (en) 2001-12-05 2008-08-11 Уайт Substituted benzoxazoles and analogues as estrogenic agents
US6835745B2 (en) 2002-01-15 2004-12-28 Wyeth Phenyl substituted thiophenes as estrogenic agents
CN101052641A (en) 2004-09-07 2007-10-10 惠氏公司 6H-[1]benzopyrano[4,3-b]quinolines and their use as estrogenic agents

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0629697A2 (en) * 1993-06-21 1994-12-21 Eli Lilly And Company Materials and methods for screening anti-osteoporosis agents
WO1996002565A1 (en) * 1994-07-20 1996-02-01 Celtrix Pharmaceuticals, Inc. Igf/igfbp complex for promoting bone formation and for regulating bone remodeling
WO1997031640A1 (en) * 1996-02-28 1997-09-04 Pfizer Inc. Combination therapy for osteoporosis
WO1998025623A1 (en) * 1996-12-09 1998-06-18 Merck & Co., Inc. Methods and compositions for preventing and treating bone loss

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0629697A2 (en) * 1993-06-21 1994-12-21 Eli Lilly And Company Materials and methods for screening anti-osteoporosis agents
WO1996002565A1 (en) * 1994-07-20 1996-02-01 Celtrix Pharmaceuticals, Inc. Igf/igfbp complex for promoting bone formation and for regulating bone remodeling
WO1997031640A1 (en) * 1996-02-28 1997-09-04 Pfizer Inc. Combination therapy for osteoporosis
WO1998025623A1 (en) * 1996-12-09 1998-06-18 Merck & Co., Inc. Methods and compositions for preventing and treating bone loss

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BARKHEM ET AL: "Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists", MOLECULAR PHARMACOLOGY, vol. 54, no. 1, August 1998 (1998-08-01), pages 105 - 111, XP000978331 *
EVANS, GLENDA ET AL: "The effects of raloxifene on tibia histomorphometry in ovariectomized rats", ENDOCRINOLOGY (1994), 134(5), 2283-8, XP000563692 *
EVANS, GLENDA L. ET AL: "Raloxifene inhibits bone turnover and prevents further cancellous bone loss in adult ovariectomized rats wit established osteopenia", ENDOCRINOLOGY (1996), 137(10), 4139-4144, XP002088886 *
FRITZ, P. C. ET AL: "Tamoxifen attenuates the effects of exogenous glucocorticoid on bone formation and growth in piglets", ENDOCRINOLOGY (1998), 139(8), 3399-3403, XP000979648 *
LABRIE, FERNAND ET AL: "EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium", J. STEROID BIOCHEM. MOL. BIOL. (1999), 69(1-6), 51-84, XP000978361 *
NILSSON ET AL: "ER-beta: A novel estrogen receptor offers the potential for new drug development", TRENDS ENDOCRINOL. METAB., vol. 9, no. 10, 1998, pages 387 - 395, XP000978334 *

Also Published As

Publication number Publication date
AU5545400A (en) 2001-01-02
EP1185287A2 (en) 2002-03-13
CA2376441A1 (en) 2000-12-21
GB9913649D0 (en) 1999-08-11
WO2000076529A2 (en) 2000-12-21

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