JP2002512690A - 核タンパク質/核レセプターの相互作用のインヒビター - Google Patents
核タンパク質/核レセプターの相互作用のインヒビターInfo
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- JP2002512690A JP2002512690A JP54674498A JP54674498A JP2002512690A JP 2002512690 A JP2002512690 A JP 2002512690A JP 54674498 A JP54674498 A JP 54674498A JP 54674498 A JP54674498 A JP 54674498A JP 2002512690 A JP2002512690 A JP 2002512690A
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.a)核タンパク質の配列モチーフである第1の領域および b)前記の配列モチーフに結合することにより核タンパク質との相互作用を可能 にする核レセプターの一部である第2の領域間の相互作用を低下させることを可 能にするインヒビター化合物を同定する方法において、 核タンパク質は遺伝子発現の制御に関係するリガンド結合核レセプターおよび転 写開始複合体間の相互作用の役割を担う架橋因子であり、 核レセプターは転写因子であり、 配列モチーフは標的遺伝子の活性化または抑制のプロセスの一部としてリガンド 結合核レセプターに結合する核タンパク質の重要な構造要素である短いアミノ酸 配列であり、その際 i)候補となるインヒビター化合物、 ii)リガンド結合核レセプターまたはこの請求項中の前記のb)で定義した第 2の領域を有するその断片、 iii)核タンパク質の配列モチーフを有する断片を使用し、かつ iv)ii)およびiii)間の相互作用の阻害の存在または不在を検出するこ とを特徴とする、インヒビ ター化合物の同定方法。 2.配列モチーフはB1XXLL(式中B1は任意の天然疎水性アミノ酸であり 、Lはロイシンであり、かつXは独立に任意の天然アミノ酸である)である、請 求項1記載の方法。 3.B1はロイシンまたはバリンである請求項2記載の方法。 4.B1はロイシンである請求項3記載の方法。 5.配列モチーフが更にB2B1XXLL(式中、B2は疎水性アミノ酸である )である請求項2から4までのいずれか1項記載の方法。 6.B2はイソロイシン、ロイシン、メチオニン、フェニルアラニン、トリプ トファン、チロシンおよびバリンからなる群から選択される請求項5記載の方法 。 7.核タンパク質はコアクチベーターである請求項1から6までのいずれか1 項記載の方法。 8.コアクチベーターはRIP140、SRC−1、TIF2、CBP、p3 00、TIF1、Trip1、Trip2、Tr1p3、Trip4、Trip 5、Trip8、Trip9、p/CIP、ARA70およびTrip230か らなる群から選択される請求項7記載の方法。 9.転写因子はステロイドホルモンレセプターである請求項1から6までのい ずれか1項記載の方法。 10.ステロイドホルモンレセプターはエストロゲ ンレセプター、プロゲステロンレセプター、アンドロゲンレセプターおよびグル ココルチコイドレセプターからなる群から選択される請求項9記載の方法。 11.ステロイドホルモンレセプターはエストロゲンレセプターである請求項 10記載の方法。 12.方法は2−ハイブリッドアッセイ系の形である請求項1から11までの いずれか1項記載の方法。 13.候補となるインヒビターは請求項2から6までのいずれか1項記載の配 列モチーフに基づくペプチドライブラリーの形である請求項1から12までのい ずれか1項記載の方法。 14.請求項1から13までのいずれか1項記載の方法により同定される新規 インヒビターにおいて、該インヒビターが、 a)核タンパク質上の配列モチーフである第1の領域および b)前記の配列モチーフに結合することにより核タンパク質との相互作用を可能 にする核レセプターの一部である第2の領域間の相互作用を低下させ、 この際 核タンパク質は遺伝子発現の制御に関係するリガンド結合核レセプターおよび転 写開始複合体間の相互作用の役割を担う架橋因子であり、 核レセプターは転写因子であり、 配列モチーフは標的遺伝子の活性化または抑制のプロ セスの一部としてリガンド結合核レセプターに結合する核タンパク質の重要な構 造要素である短いアミノ酸配列である、 ことを特徴とする新規インヒビター。 15.請求項1から6までのいずれか1項記載の配列モチーフを有する15ア ミノ酸残基未満のペプチドである請求項14記載のインヒビター。 16.PQAQQKSLLQQLLT(SEQ ID NO:2)、KLVQ LLTTT(SEQ ID NO:3)、ILHRLLQE(SEQ ID N O:4)およびLLQQLLTE(SEQ ID NO:5)からなる群から選 択される請求項15記載のインヒビター。 17.核タンパク質上の配列モチーフに特異的に結合する抗体を含む請求項1 4記載のインヒビター。 18.請求項14から17までのいずれか1項記載のインヒビターまたはその 製薬学的に認容性の塩を製薬学的に認容性の希釈剤またはキャリヤーと組み合わ せて含有する医薬品組成物。 19.核タンパク質中の核レセプター相互作用ドメインをマッピングする方法 において、請求項1から6までのいずれか1項記載の配列モチーフの存在に関し て核タンパク質の配列を分析し、相互作用ドメインまたは候補となる相互作用ド メインを同定することを特徴とするマッピング方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GB9708676.3 | 1997-04-30 | ||
GBGB9708676.3A GB9708676D0 (en) | 1997-04-30 | 1997-04-30 | Chemical compounds |
PCT/GB1998/001238 WO1998049561A1 (en) | 1997-04-30 | 1998-04-28 | Inhibitors of nuclear protein/nuclear receptor interaction |
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JP2007143973A Division JP4206420B2 (ja) | 1997-04-30 | 2007-05-30 | 核タンパク質/核レセプターの相互作用のインヒビター |
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JP2002512690A true JP2002512690A (ja) | 2002-04-23 |
JP2002512690A5 JP2002512690A5 (ja) | 2005-11-24 |
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JP54674498A Pending JP2002512690A (ja) | 1997-04-30 | 1998-04-28 | 核タンパク質/核レセプターの相互作用のインヒビター |
JP2007143973A Expired - Fee Related JP4206420B2 (ja) | 1997-04-30 | 2007-05-30 | 核タンパク質/核レセプターの相互作用のインヒビター |
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JP2007143973A Expired - Fee Related JP4206420B2 (ja) | 1997-04-30 | 2007-05-30 | 核タンパク質/核レセプターの相互作用のインヒビター |
Country Status (11)
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EP (1) | EP0980526B1 (ja) |
JP (2) | JP2002512690A (ja) |
AT (1) | ATE338276T1 (ja) |
AU (1) | AU7220798A (ja) |
CY (1) | CY1105809T1 (ja) |
DE (1) | DE69835741T2 (ja) |
DK (1) | DK0980526T3 (ja) |
ES (1) | ES2271993T3 (ja) |
GB (1) | GB9708676D0 (ja) |
PT (1) | PT980526E (ja) |
WO (1) | WO1998049561A1 (ja) |
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US7101681B1 (en) * | 1997-11-21 | 2006-09-05 | Amgen, Inc. | Nuclear hormone receptor drug screens |
US6303576B1 (en) * | 1999-04-21 | 2001-10-16 | Adherex Technologies Inc. | Compounds and methods for modulating β-catenin mediated gene expression |
US20040137441A1 (en) * | 2003-01-15 | 2004-07-15 | Isis Pharmaceuticals Inc. | Modulation of thyroid hormone receptor interactor 3 expression |
GB0215496D0 (en) * | 2002-07-04 | 2002-08-14 | Imp College Innovations Ltd | Screening for anti-ovulatory compounds |
WO2015110440A1 (en) * | 2014-01-22 | 2015-07-30 | Koninklijke Philips N.V. | Improved stratification of patients for assessing the suitability of a therapy |
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EP0912896A4 (en) * | 1996-05-31 | 2004-08-18 | Basf Ag | IDENTIFICATION OF ULTRASPIRACLE INHIBITORS |
EP1865060B1 (en) * | 1996-07-12 | 2010-11-17 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Transcriptional Intermediary Factor-2 |
US5877282A (en) * | 1996-09-20 | 1999-03-02 | Bristol-Myers Squibb Company | Peptide inhibitors of nuclear protein translocation having nuclear localization sequences and methods of use thereof |
-
1997
- 1997-04-30 GB GBGB9708676.3A patent/GB9708676D0/en active Pending
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1998
- 1998-04-28 DK DK98919329T patent/DK0980526T3/da active
- 1998-04-28 WO PCT/GB1998/001238 patent/WO1998049561A1/en active IP Right Grant
- 1998-04-28 EP EP98919329A patent/EP0980526B1/en not_active Expired - Lifetime
- 1998-04-28 PT PT98919329T patent/PT980526E/pt unknown
- 1998-04-28 AT AT98919329T patent/ATE338276T1/de active
- 1998-04-28 DE DE69835741T patent/DE69835741T2/de not_active Expired - Lifetime
- 1998-04-28 JP JP54674498A patent/JP2002512690A/ja active Pending
- 1998-04-28 AU AU72207/98A patent/AU7220798A/en not_active Abandoned
- 1998-04-28 ES ES98919329T patent/ES2271993T3/es not_active Expired - Lifetime
-
2006
- 2006-11-29 CY CY20061101715T patent/CY1105809T1/el unknown
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2007
- 2007-05-30 JP JP2007143973A patent/JP4206420B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
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DE69835741D1 (de) | 2006-10-12 |
EP0980526A1 (en) | 2000-02-23 |
JP4206420B2 (ja) | 2009-01-14 |
DE69835741T2 (de) | 2007-09-13 |
CY1105809T1 (el) | 2011-02-02 |
ATE338276T1 (de) | 2006-09-15 |
PT980526E (pt) | 2006-12-29 |
DK0980526T3 (da) | 2006-12-04 |
GB9708676D0 (en) | 1997-06-18 |
ES2271993T3 (es) | 2007-04-16 |
AU7220798A (en) | 1998-11-24 |
WO1998049561A1 (en) | 1998-11-05 |
EP0980526B1 (en) | 2006-08-30 |
JP2007304102A (ja) | 2007-11-22 |
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