KR950000875A - 골다공증 치료제의 탐색 물질 및 탐색방법 - Google Patents
골다공증 치료제의 탐색 물질 및 탐색방법 Download PDFInfo
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Abstract
본 발명은 골다공증 치료제 및 혈청 지질 강하제의 탐색방법에 관한 것이다. 본 발명은 "랄록시펜 반응 요소"로 나타내는 신규한 조절 요소를 포함하는 포유동물 형질전환 성장 인자 β유전자의 프로모터 영역으로부터의 핵산의 단리, 클로닝 및 사용방법에 관한 것이다. 본 발명은 또한 상기 랄록시펜 반응 요소가 리포터 유전자의 전사를 조절하도록 상기 리포터 유전자에 작동적으로 결합된 상기 요소를 함유하는 진핵 세포를 포함한다. 본 발명은 기존의 골다공증 치료 섭생과 관련된 유해하거나 바람직하지 못한 부작용이 없는, 상기와 같은 랄록시펜 반응 요소에 작동적으로 결합된 유전자의 전사를 유도하는 골다공증 치료제의 탐색방법을 제공한다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 TGFβ-1 유전자의 프로모터 영역을 도시한다. 제2도는 TGFβ-2 유전자의 프로모터 영역을 도시한다. 제3도는 TGFβ-3 유전자의 프로모터 영역을 도시한다.
Claims (6)
- TGFβ 유전자(여기에서 인간 TGFβ 유전자는 TGFβ-2 또는 TGFβ-3이다)의 프로모터 영역으로부터 단리된 랄록시펜(raloxifene) 반응 요소를 포함하는 핵산.
- (a) 포유동물 프로모터의 랄록시펜 반응 요소로부터 전사를 유도하는 화합물의 능력을 분석하는 단계; (b) 랄록시펜 반응 요소를 갖지 않는 포유동물 프로모터로부터 전사를 유도할 수 없는 화합물을 분석하는 단계; (c) 에스트로겐 반응성 프로모터로부터 전사를 유도할 수 없는 화합물을 분석하는 단계; 및 (d) 에스트로겐의 존재하에서 에스트로겐 반응성 프로모터로부터의 에스트로겐-유도된 전사를 억제하는 화합물의 능력을 분석하는 단계를 포함하고, 포유동물 프로모터의 랄록시펜 반응 요소로부터 전사를 유도할 수 있고, 비-특이적인 전사 유도물질은 아니며, 포유동물 프로모터의 에스트로겐 반응 요소로부터 전사를 유도할 수 없고, 항에스트로겐 또는 비에스트로겐 화합물인 다수의 화합물을 확인함을 포함하는 골다공증 치료제로서의 가능성을 갖는 화합물을 확인하기 위한 다수 화합물의 탐색방법.
- 에스트로겐 수용체에 결합시, TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 포유동물에게 투여함을 포함하는 상기 포유동물의 골형성 유도 방법;(Ⅰ)상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서 선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
- 에스트로겐 수용체에 결합시, TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 투여함을 포함하는 골다공증의 치료 방법;(Ⅰ)상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서 선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
- 에스트로겐 수용체에 결합시, TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 투여함을 포함하는 골균열의 치료 방법;(Ⅰ)상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
- (a) TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하고; (b) 랄록시펜 반응 요소를 갖지 않는 포유동물 프로모터로부터는 전사를 유도하지 않으며; (c) 에스트로겐 반응성 프로모터로부터 전사를 유도하지 않고; (d) 에스트로겐의 존재하에서 에스트로겐 반응성 프로모터로부터의 에스트로겐 유도된 전사를 억제하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 포유동물에게 투여함을 포함하는 상기 포유동물의 골형성 유도 방법;(Ⅰ)상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서 선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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Application Number | Priority Date | Filing Date | Title |
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US08/081,610 US5445941A (en) | 1993-06-21 | 1993-06-21 | Method for screening anti-osteoporosis agents |
US08/081,610 | 1993-06-21 | ||
US24699094A | 1994-05-18 | 1994-05-18 | |
US08/246,990 | 1994-05-18 |
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KR950000875A true KR950000875A (ko) | 1995-01-03 |
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EP (1) | EP0629697A3 (ko) |
JP (1) | JPH07184661A (ko) |
KR (1) | KR950000875A (ko) |
CN (1) | CN1102437A (ko) |
AU (2) | AU677319B2 (ko) |
BR (1) | BR9402480A (ko) |
CA (1) | CA2126294A1 (ko) |
CZ (1) | CZ147594A3 (ko) |
FI (1) | FI942958A (ko) |
HU (1) | HUT70326A (ko) |
IL (1) | IL109990A (ko) |
NO (1) | NO942313L (ko) |
PL (1) | PL177706B1 (ko) |
YU (1) | YU39594A (ko) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR100504042B1 (ko) * | 2002-10-23 | 2005-08-01 | 신경주 | 자가 세차장치를 구비한 자동차 |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6515009B1 (en) | 1991-09-27 | 2003-02-04 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5811447A (en) | 1993-01-28 | 1998-09-22 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6251920B1 (en) | 1993-05-13 | 2001-06-26 | Neorx Corporation | Prevention and treatment of cardiovascular pathologies |
US6395494B1 (en) | 1993-05-13 | 2002-05-28 | Neorx Corporation | Method to determine TGF-β |
US6491938B2 (en) | 1993-05-13 | 2002-12-10 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5723291A (en) * | 1993-09-01 | 1998-03-03 | The Regents Of The University Of California | Methods for screening compounds for estrogenic activity |
US6156723A (en) | 1993-09-01 | 2000-12-05 | The Regents Of The University Of California | Compositions comprising inhibitors of estrogen response |
US5552415A (en) * | 1993-12-21 | 1996-09-03 | Eli Lilly And Company | Method of inhibiting Alzheimer's Disease |
US6083690A (en) * | 1995-06-02 | 2000-07-04 | Osteoscreen, Inc. | Methods and compositions for identifying osteogenic agents |
JP3761628B2 (ja) * | 1995-07-14 | 2006-03-29 | 住友化学株式会社 | 植物プロモーターおよびその利用 |
AU5558498A (en) * | 1996-11-22 | 1998-06-22 | Akzo Nobel N.V. | Bmp-4 promoter and use thereof in screening of therapeutic agents for the prevention and/or treatment of osteoporosis |
AU6959898A (en) * | 1997-04-11 | 1998-11-11 | David J. Grainger | Compounds and therapies for the prevention of vascular and non-vascular pathol ogies |
DE69833822D1 (de) * | 1998-10-01 | 2006-05-11 | Giovanni Gambaro | Substanzen zur Vorbeugung von krankhafter TGF-beta Überexpression und Methoden derer Ermittlung |
GB9822682D0 (en) * | 1998-10-16 | 1998-12-09 | Gemini Research Limited | Diagnostic method and apparatus based on polymorphism in a TGF-B-Gene |
GB9913649D0 (en) * | 1999-06-11 | 1999-08-11 | Karobio Ab | Estrogen receptor |
WO2002020759A2 (en) * | 2000-09-08 | 2002-03-14 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A non-steroidal anti-inflammatory drug activated gene with anti-tumorigenic properties |
CN106841258A (zh) * | 2016-12-30 | 2017-06-13 | 遵义医学院附属医院 | 一种筛选用于促进骨愈合的药物的方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
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AU509682B2 (en) * | 1975-10-28 | 1980-05-22 | Eli Lilly And Company | 2-Aroyl-3-Phenylbenzothiophene Derivatives |
US4133814A (en) * | 1975-10-28 | 1979-01-09 | Eli Lilly And Company | 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents |
US4380635A (en) * | 1981-04-03 | 1983-04-19 | Eli Lilly And Company | Synthesis of acylated benzothiophenes |
US5071773A (en) * | 1986-10-24 | 1991-12-10 | The Salk Institute For Biological Studies | Hormone receptor-related bioassays |
US4935363A (en) * | 1987-03-30 | 1990-06-19 | Board Of Regents, The University Of Texas System | Sterol regulatory elements |
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1994
- 1994-06-13 IL IL10999094A patent/IL109990A/xx not_active IP Right Cessation
- 1994-06-14 AU AU64701/94A patent/AU677319B2/en not_active Withdrawn - After Issue
- 1994-06-15 CZ CZ941475A patent/CZ147594A3/cs unknown
- 1994-06-17 NO NO942313A patent/NO942313L/no unknown
- 1994-06-20 BR BR9402480A patent/BR9402480A/pt not_active Application Discontinuation
- 1994-06-20 PL PL94303915A patent/PL177706B1/pl unknown
- 1994-06-20 EP EP94304432A patent/EP0629697A3/en not_active Withdrawn
- 1994-06-20 JP JP6137287A patent/JPH07184661A/ja not_active Withdrawn
- 1994-06-20 FI FI942958A patent/FI942958A/fi unknown
- 1994-06-20 KR KR1019940013849A patent/KR950000875A/ko not_active Application Discontinuation
- 1994-06-20 YU YU39594A patent/YU39594A/sh unknown
- 1994-06-20 HU HU9401851A patent/HUT70326A/hu unknown
- 1994-06-20 CA CA002126294A patent/CA2126294A1/en not_active Abandoned
- 1994-06-20 CN CN94106717A patent/CN1102437A/zh active Pending
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1997
- 1997-07-17 AU AU28710/97A patent/AU2871097A/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR100504042B1 (ko) * | 2002-10-23 | 2005-08-01 | 신경주 | 자가 세차장치를 구비한 자동차 |
Also Published As
Publication number | Publication date |
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AU6470194A (en) | 1994-12-22 |
YU39594A (sh) | 1997-03-07 |
NO942313L (no) | 1994-12-22 |
BR9402480A (pt) | 1995-01-25 |
IL109990A0 (en) | 1994-10-07 |
CA2126294A1 (en) | 1994-12-22 |
CN1102437A (zh) | 1995-05-10 |
EP0629697A2 (en) | 1994-12-21 |
HU9401851D0 (en) | 1994-09-28 |
AU677319B2 (en) | 1997-04-17 |
JPH07184661A (ja) | 1995-07-25 |
PL177706B1 (pl) | 2000-01-31 |
CZ147594A3 (en) | 1995-06-14 |
FI942958A (fi) | 1994-12-22 |
HUT70326A (en) | 1995-09-28 |
PL303915A1 (en) | 1995-01-09 |
AU2871097A (en) | 1997-09-25 |
EP0629697A3 (en) | 1995-04-19 |
FI942958A0 (fi) | 1994-06-20 |
IL109990A (en) | 1999-06-20 |
NO942313D0 (no) | 1994-06-17 |
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