Department of Advanced Protein Science, Institute of Microbial Technology, Chandigarh 160036, India.
Future Med Chem. 2019 Nov;11(21):2803-2819. doi: 10.4155/fmc-2019-0096. Epub 2019 Nov 8.
The druggability of epigenetic targets has prompted researchers to develop small-molecule therapeutics. However, no systematic assessment has ever been done to investigate the chemical space of epigenetic modulators. Herein, we report a comprehensive chemoinformatic analysis of epigenetic ligands from EpiDBase, HEMD, ChEMBL and PubChem databases. Nearly, 0.45 × 10 ligands were analyzed for assay interference compounds, target profiling, drug-like properties and hit prioritization. After eliminating approximately 96,000 problematic compounds, the remaining 0.36 × 10 compounds were studied for their physicochemical distributions, principal component analysis and hit prioritization. More than 30% of assay interference compounds were determined for many proteins. This systematic assessment of epigenetic ligands will help in the enrichment of screening libraries with high-quality compounds and thus, the generation of efficacious drug candidates.
表观遗传学靶点的成药性促使研究人员开发了小分子治疗药物。然而，迄今尚未进行系统评估以研究表观遗传调节剂的化学空间。在此，我们报告了来自 EpiDBase、HEMD、ChEMBL 和 PubChem 数据库的表观遗传配体的全面计算化学分析。将近 4500 万个配体被分析用于检测干扰化合物、靶标分析、类药性和命中优先级。消除约 96000 个有问题的化合物后，剩余的 3600 万个化合物被研究其物理化学分布、主成分分析和命中优先级。许多蛋白质的测定结果表明，有 30%以上的测定干扰化合物。对表观遗传配体的这种系统评估将有助于用高质量化合物丰富筛选文库，从而生成有效的候选药物。
