JP2006030037A5 - - Google Patents

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JP2006030037A5
JP2006030037A5 JP2004210868A JP2004210868A JP2006030037A5 JP 2006030037 A5 JP2006030037 A5 JP 2006030037A5 JP 2004210868 A JP2004210868 A JP 2004210868A JP 2004210868 A JP2004210868 A JP 2004210868A JP 2006030037 A5 JP2006030037 A5 JP 2006030037A5
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Japan
Prior art keywords
nuclear receptor
compound
candidate compound
modulates
covalently bound
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JP2004210868A
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Japanese (ja)
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JP4525221B2 (en
JP2006030037A (en
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Claims (9)

核内受容体を調節する化合物を同定する方法であって、該方法は：
A）候補化合物を提供する工程； および
B）該候補化合物が、該核内受容体中のシステインと共有結合するかどうかを判定する工程であって、共有結合すると判定された候補化合物を、核内受容体を調節する化合物であると同定する工程
を包含する方法。 A method of identifying a compound that modulates a nuclear receptor, the method comprising:
A) providing a candidate compound; and
B) determining whether the candidate compound is covalently bound to cysteine in the nuclear receptor, wherein the candidate compound determined to be covalently bound is a compound that modulates a nuclear receptor A method comprising the step of identifying. 請求項1に記載される方法によって、特定された化合物を含む核内受容体の調節のための組成物であって、該化合物は、以下の式：
（化2）
Ｒ1−ＣＨ＝ＣＨ−（Ｃ＝Ｏ）−Ｒ2−Ｒ3または
Ｒ1−（Ｃ＝Ｏ）−ＣＨ＝ＣＨ−Ｒ2−Ｒ3
という構造を有し、ここで、Ｒ1は、最短距離を結ぶ炭素数の最大値が1〜13個の、置換されていてもよい飽和または不飽和の炭化水素基であり、Ｒ2は、置換されていてもよい飽和または不飽和の炭化水素基であり、Ｒ3は、水素または置換されていてもよい、カルボニル基、水酸基、アミド基およびチオール基からなる群より選択される置換基を含む一価の置換基であり、ここでＲ2とＲ3とは、含まれる炭素について、最短距離を結ぶ炭素数の最大値が4〜14個である組成物。 A composition for modulation of a nuclear receptor comprising a specified compound according to the method of claim 1, wherein the compound has the formula:
(Chemical 2)
R 1 —CH═CH— (C═O) —R 2 —R 3 or R 1 — (C═O) —CH═CH—R 2 —R 3
Where R 1 is an optionally substituted saturated or unsaturated hydrocarbon group having a maximum of 1 to 13 carbon atoms connecting the shortest distance, and R 2 is A saturated or unsaturated hydrocarbon group which may be substituted, and R 3 represents a substituent selected from the group consisting of hydrogen or an optionally substituted carbonyl group, hydroxyl group, amide group and thiol group; A composition in which R 2 and R 3 are monovalent substituents, and the maximum number of carbon atoms connecting the shortest distance is 4 to 14 for the contained carbon. 請求項1に記載される方法によって、特定された化合物を含む、核内受容体に起因する疾患、障害または状態の処置、予防または予後のための組成物であって、該化合物は、以下の式：
（化3）
Ｒ1−Ｃ＝Ｃ−（Ｃ＝Ｏ）−Ｒ2−Ｒ3または
Ｒ1−（Ｃ＝Ｏ）−Ｃ＝Ｃ−Ｒ2−Ｒ3
という構造を有し、ここで、Ｒ1は、最短距離を結ぶ炭素数の最大値が1〜13個の、置換されていてもよい飽和または不飽和の炭化水素基であり、Ｒ2は、置換されていてもよい飽和または不飽和の炭化水素基であり、Ｒ3は、水素または置換されていてもよい、カルボニル基、水酸基、アミド基およびチオール基からなる群より選択される置換基を含む一価の置換基であり、ここでＲ2とＲ3とは、含まれる炭素について、最短距離を結ぶ炭素数の最大値が4〜14個である組成物。 A composition for the treatment, prevention or prognosis of a disease, disorder or condition caused by a nuclear receptor comprising a compound identified by the method of claim 1, wherein the compound comprises: formula:
(Chemical formula 3)
R 1 —C═C— (C═O) —R 2 —R 3 or R 1 — (C═O) —C═C—R 2 —R 3
Where R 1 is an optionally substituted saturated or unsaturated hydrocarbon group having a maximum of 1 to 13 carbon atoms connecting the shortest distance, and R 2 is A saturated or unsaturated hydrocarbon group which may be substituted, and R 3 represents a substituent selected from the group consisting of hydrogen or an optionally substituted carbonyl group, hydroxyl group, amide group and thiol group; A composition in which R 2 and R 3 are monovalent substituents, and the maximum number of carbon atoms connecting the shortest distance is 4 to 14 for the contained carbon. 1）標的生体分子と、リガンドとを混合して混合物を生成する工程；
2）蛍光標識マレイミドを該混合物に加える工程；
3）該混合物において、該標的生体分子と該蛍光標識マレイミドとの結合を検出する工程
を包含する、該標的生体分子に対するリガンドの結合能を定量する方法。 1) A step of mixing a target biomolecule and a ligand to form a mixture;
2) adding fluorescently labeled maleimide to the mixture;
3) A method for quantifying the ability of a ligand to bind to the target biomolecule, comprising the step of detecting the binding between the target biomolecule and the fluorescently labeled maleimide in the mixture. 核内受容体を調節する化合物を同定するシステムであって、該システムは：
A）候補化合物が、該核内受容体中のシステインと共有結合するかどうかを判定する手段； および
B）共有結合すると判定された候補化合物を、核内受容体を調節する化合物であると算出する手段
を備えるシステム。 A system for identifying a compound that modulates a nuclear receptor, the system comprising:
A) means for determining whether a candidate compound covalently binds to a cysteine in the nuclear receptor;
B) A system comprising means for calculating a candidate compound determined to be covalently bound as a compound that modulates a nuclear receptor. 核内受容体を調節する化合物を同定するために用いられる、化合物と、該核内受容体との共有結合を測定するためのキットであって、
A）該核内受容体と不可逆的に共有結合することが分かっているリガンド； および
B）共有結合しないリガンドの結合を測定するための手順を記載する指示書
を備えるキット。 A kit for measuring the covalent bond between a compound and the nuclear receptor, which is used to identify a compound that modulates the nuclear receptor,
A) a ligand known to irreversibly covalently bind to the nuclear receptor;
B) A kit with instructions describing the procedure for measuring the binding of non-covalently bound ligands. 核内受容体を調節する化合物を同定する方法をコンピュータに実行させるプログラムであって、該方法は：
A）候補化合物の立体構造データを提供する工程； および
B）該候補化合物が、該核内受容体中のシステインと共有結合するかどうかを判定する工程であって、共有結合すると判定された候補化合物を、核内受容体を調節する化合物であると同定する工程
を包含するプログラム。 A program that causes a computer to execute a method of identifying a compound that modulates a nuclear receptor, the method comprising:
A) providing the three-dimensional structure data of the candidate compound; and
B) determining whether the candidate compound is covalently bound to cysteine in the nuclear receptor, wherein the candidate compound determined to be covalently bound is a compound that modulates a nuclear receptor A program that includes the step of identifying. 核内受容体を調節する化合物を同定する方法をコンピュータに実行させるプログラムを格納する記録媒体であって、該方法は：
A）候補化合物の立体構造データを提供する工程； および
B）該候補化合物が、該核内受容体中のシステインと共有結合するかどうかを判定する工程であって、共有結合すると判定された候補化合物を、核内受容体を調節する化合物であると同定する工程
を包含する記録媒体。 A recording medium storing a program for causing a computer to execute a method for identifying a compound that modulates a nuclear receptor, the method comprising:
A) providing the three-dimensional structure data of the candidate compound; and
B) determining whether the candidate compound is covalently bound to cysteine in the nuclear receptor, wherein the candidate compound determined to be covalently bound is a compound that modulates a nuclear receptor A recording medium including an identifying step. 候補化合物が、核内受容体のアゴニストであるかまたはアンタゴニストであるかどうかを判定する方法であって、該方法は：
A）候補化合物を提供する工程； および
B）該候補化合物が、該核内受容体中のシステインと共有結合するかどうかを判定し、共有結合すると判定された候補化合物を選択する工程；
C）転写因子認識配列と作動可能に連結されるレポーターをコードする核酸配列を含む核酸構築物と、該選択された核内受容体とを含む系において、該候補化合物の活性を判定する工程であって、該レポーターの発現が増強される場合、該候補化合物は該核内受容体のアゴニストと判定し、該レポーターの発現が減少する場合、該候補化合物は該核内受容体のアンタゴニストと判定する工程
を包含する方法。 A method for determining whether a candidate compound is an agonist or antagonist of a nuclear receptor, the method comprising:
A) providing a candidate compound; and
B) determining whether or not the candidate compound is covalently bound to cysteine in the nuclear receptor, and selecting the candidate compound determined to be covalently bound;
C) determining the activity of the candidate compound in a system comprising a nucleic acid construct comprising a nucleic acid sequence encoding a reporter operably linked to a transcription factor recognition sequence and the selected nuclear receptor. When the reporter expression is enhanced, the candidate compound is determined to be an agonist of the nuclear receptor, and when the reporter expression is decreased, the candidate compound is determined to be an antagonist of the nuclear receptor. A method comprising the steps.
JP2004210868A 2004-07-16 2004-07-16 Receptor ligand identification method Expired - Fee Related JP4525221B2 (en)

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JP2006030037A JP2006030037A (en) 2006-02-02
JP2006030037A5 true JP2006030037A5 (en) 2007-08-23
JP4525221B2 JP4525221B2 (en) 2010-08-18

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2181710A1 (en) * 2008-10-28 2010-05-05 Phenex Pharmaceuticals AG Ligands for modulation of orphan receptor-gamma (NR1F3) activity
JP2011037739A (en) * 2009-08-10 2011-02-24 Pola Chemical Industries Inc Composition
WO2014026330A1 (en) * 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF

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EP1407767A4 (en) * 2001-06-18 2007-01-24 Yamada Sachiko Pparg agonistic medicinal compositions
JP3888998B2 (en) * 2001-07-17 2007-03-07 帝人株式会社 Method for selecting substance and drug characterized by measuring PPARδ activation action
GB0119920D0 (en) * 2001-08-15 2001-10-10 Pfizer Ltd New use

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