ユビキチンシステムは,タンパク質キナーゼと同じくらい多くの薬物の標的を提供できるのでしょうか?
Philip Cohen1, Marianna Tcherpakov
1Sir James Black Centre, Dundee, Scotland, UK. p.cohen@dundee.ac.uk
Cell
|November 30, 2010
まとめ
タンパク質のユビキチネーションを標的とした薬剤の発見は,タンパク質キナーゼに遅れをとっている. この展望は,遅延の理由,現在の薬,およびがんやその他の疾患に対するユビキチン系薬剤発見を進めるための将来のアプローチを探求します.
科学分野:
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
- ドラッグ・ディスカバリー・ドラッグ・ディスカバリー
背景:
- タンパク質のリン酸化とユビキチネーションは,重要な細胞プロセスである.
- これらのプロセスの不調は,がんやその他の病気と関連しています.
- タンパク質キナーゼは,ユビキチン系成分とは異なり,確立された薬物標的です.
研究 の 目的:
- ユビキチン系薬剤発見における遅い進歩の理由を分析する.
- ユビキチン系を標的とする既存の薬物の見直しを行う.
- この分野を普及させるための将来の戦略を提案する.
主な方法:
- 薬剤発見パイプラインの文献レビューと分析.
- キナーゼとユビキチンシステムの薬物開発の比較分析.
- 新興治療戦略の議論.
主要な成果:
- ユビキチン標的薬の開発の遅延に寄与する重要な要因を特定しました.
- カタログ化された現在の薬物とその作用機構.
- 治療的可能性のある新しいアプローチを強調した.
結論:
- ユビキチン系は,治療目標の豊富な,まだ未開発の源を表しています.
- 特定の課題を克服することで,この分野における薬物開発を加速させることができます.
- ユビキチンベースの治療法の潜在力を実現するために,将来の研究と投資は極めて重要です.
関連する概念動画
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:18The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
01:26Targets for Drug Action: Overview
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include: