JP6578046B1 - Pde5阻害用医薬組成物及びpde5阻害用食品組成物 - Google Patents
Pde5阻害用医薬組成物及びpde5阻害用食品組成物 Download PDFInfo
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Abstract
Description
5-アセチル-1-ベンジルピロリジン-2-オンのPDE5阻害活性を評価するため、蛍光偏光法によるPDE5阻害アッセイを実施した。アッセイには、IMAP(商標)アッセイキット(モレキュラーデバイス社製、カタログ番号R8127)を使用した。評価はすべて二重検定で実施した。ナノ粒子上に固定した金属配位錯体によるリン酸塩の高親和性結合にもとづいて、アッセイした。IMAP結合試薬は、ホスホジエステラーゼによりcGMPから生じたヌクレオチド一リン酸のリン酸基と複合体を形成する。蛍光偏光の検出により、結合すると、リン酸含有分子の分子運動速度に変化が生じ、結果として基質にラベルした蛍光の偏光が増大する。
1)基質溶液
2.5mM Tris−HCl、2mM MgCl2、0.01% NaN3、0.02% BSAを含むIMAP反応緩衝液中でフルオレセイン標識cGMP(100nM)を調製した。
2)酵素溶液
バキュロウイルスを用いて昆虫細胞で発現・精製させたヒトPDE5触媒ドメインをIMAP反応緩衝液中に調製した。
3)IMAP結合溶液
IMAP結合試薬をIMAP反応緩衝液中で調製した。
被験化合物をジメチルスルホキシドに溶解した。
(試験方法及び測定方法)
1)96ウェルブラックプレートに被験化合物溶液、基質溶液、酵素溶液を1ウェルあたり各10μLずつ添加した(ジメチルスルホキシドの最終濃度は3%)。
2)遮光かつ37℃で40分間インキュベートした。
3)IMAP結合溶液を1ウェルあたり60μLずつ添加した。
4)マルチラベルリーダー(パーキンエルマ一社製、Victor3)で各ウェルの485nm/530nm ex/emで蛍光偏光を測定した。
5)被験化合物に代えてジメチルスルホキシドを添加し、他は前記と同じ操作を実施して、その結果をコントロールとした。
6)酵素溶液に代えてIMAP反応緩衝液を添加し、他は前記と同じ操作を実施して、その結果をバックグラウンドとした。
PDE5限害率(%)は下記の式により算出した。結果は二重検定の平均とした。
PDE5阻害率(%)={1−(被験化合物の蛍光偏光値−バックグラウンドの蛍光偏光値)/(コントロールの蛍光偏光値−バックグラウンドの蛍光偏光値)}×100
統計解析ソフトGraphPad Prismを用いてデータ解析した。50%阻害濃度(IC50)値は、0.001〜100mg/mLの化合物濃度の存在下で酵素活性を測定し、その後、蛍光偏光値に対する化合物濃度をプロットした用量反応曲線から求めた。
5-アセチル-1-ベンジルピロリジン-2-オンのIC50値は33.7mg/mLであった。
PDE5阻害剤として知られるシルデナフィルを参照被験化合物として、他は本願化合物と同じ条件で同じ操作を実施して得られたIC50値は20.6nMであった。本試験方法における適正範囲は約5〜50nMであることから、アッセイの妥当性が示された。
Claims (2)
- 5-アセチル-1-ベンジルピロリジン-2-オンを有効成分として含有してなるPDE5阻害用医薬組成物。
- 5-アセチル-1-ベンジルピロリジン-2-オンを有効成分として含有してなるPDE5阻害用食品組成物。
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Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
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JP6962630B1 (ja) * | 2021-04-01 | 2021-11-05 | Towa Corporation 株式会社 | 筋肥大促進用医薬組成物及び食品組成物 |
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