相关实验视频
Updated: Jun 2, 2025

09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
6.5K
开发一流的FEM1B-招募素脱乙酶降解剂的开发
Felix Feller1, Irina Honin1, Martina Miranda1
1Department of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn institution, An der Immenburg 4, Bonn 53121, Germany.
Journal of medicinal chemistry
|January 13, 2025
概括
科学家们使用FEM1B开发了新的向蛋白质降解 (TPD) 药物,以降低基因组脱乙酶 (HDACs) 的降解. 化合物FF2049有效降解了HDAC1并增强了抗癌特性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- 有针对性的蛋白质降解 (TPD) 为传统的蛋白质抑制提供了替代方案.
- 基因组脱乙酶 (HDACs) 是癌症治疗的关键表观遗传标.
- 对于HDACs的TPD,很少有E3连接酶被利用.
研究的目的:
- 开发使用FEM1B E3酶的新型HDAC降解剂.
- 探索FEM1B招募PROTACs用于癌症治疗的潜力.
主要方法:
- 使用共价FEM1B连接体合成了12种蛋白质分解向嵌合体 (PROTACs).
- 固相支持并行合成方法.
- 评估HDAC降解效率和异形选择性.
主要成果:
- 顶级降解剂FF2049 (1g) 实现了85%的HDAC1降解,其DC50为257nM.
- 基于FEM1B的PROTAC选择性地降解了HDAC1-3,与之前的脑膜招募PROTAC不同.
- 在基于FEM1B的PROTACs中观察到增强的抗增殖特性.
结论:
- 成功开发了第一类FEM1B招募HDAC降解剂.
- 基于FEM1B的PROTAC显示出强烈而选择性的HDAC1-3降解.
- 这些新型降解剂由于增强的抗增殖作用,显示出有前途的抗癌潜力.
相关概念视频
Spreading of Chromatin Modifications
8.2K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.2K
Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
Histone Modification
13.0K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.0K
Heterochromatin
10.4K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
10.4K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
Nucleosome Remodeling
8.9K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
8.9K

