HDAC6检测器:在线应用程序用于评估化合物作为潜在的基因素脱乙酶6抑制剂
O V Tinkov1, V Y Grigorev2, L D Grigoreva3
1Department of Pharmacology and Pharmaceutical Chemistry, Medical Faculty, Shevchenko Transnistria State University, Tiraspol, Moldova.
SAR and QSAR in environmental research
|August 11, 2023
概括
本研究介绍了HDAC6检测器网络应用程序,其中包括用于识别基因素脱乙酶6抑制剂的QSAR模型. 它成功选了新的化合物,识别了强大的候选药物V-6和V-11.
科学领域:
- 药用化学 医学化学
- 计算化学计算化学
- 生物化学 生物化学
背景情况:
- 基因组脱乙酶6 (HDAC6) 在细胞分裂和亡等细胞过程中至关重要.
- HDAC6抑制剂是各种疾病的有前途的治疗药物.
- 开发有效的HDAC6抑制剂需要强大的预测模型.
研究的目的:
- 开发和验证HDAC6抑制剂的定量结构-活性关系 (QSAR) 模型.
- 创建一个可访问的网络应用程序,HDAC6检测器,用于对潜在的HDAC6抑制剂进行虚拟查.
- 评估新型酸衍生物作为潜在的HDAC6抑制剂.
主要方法:
- 为HDAC6抑制剂开发QSAR模型.
- 将QSAR模型集成到HDAC6检测器网络应用程序中.
- 使用HDAC6检测器对新型酸衍生物进行虚拟选.
- 在体外评估对HDAC6.6的抑制活性.
主要成果:
- 开发了HDAC6检测器应用程序,结合了QSAR模型和Lipinski的规则合规性检查.
- 虚拟查从一系列新型酸中确定了有希望的HDAC6抑制剂候选者.
- 化合物V-6和V-11在体外表现出强大的抑制活性,IC50值分别为0.99nM和0.81nM.
结论:
- 开发的QSAR模型和HDAC6检测器应用程序是识别潜在HDAC6抑制剂的有效工具.
- 新型酸衍生物,特别是V-6和V-11,作为针对HDAC6的治疗剂显著有前途.
相关概念视频
02:32Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
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 is an enzyme that can...
Writers
The writer is an enzyme that can...
02:38Heterochromatin
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 9th...
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 9th...
02:32Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...