当前位置: X-MOL 学术ChemMedChem › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Druggability Assessment for Selected Serine Proteases in a Pharmaceutical Industry Setting.
ChemMedChem ( IF 3.4 ) Pub Date : 2020-08-09 , DOI: 10.1002/cmdc.202000425
Leon Wehrhan 1 , Alexander Hillisch 1 , Stefan Mundt 1 , Adrian Tersteegen 1 , Katharina Meier 1
Affiliation  

Target druggability assessment is an integral part of the early target characterization and selection process in pharmaceutical industry. Here, we investigate a set of five different serine proteases from the blood coagulation cascade. The aim of this study is twofold. Firstly, leveraging the wealth of available in‐house high‐throughput screening (HTS) data, we analyze HTS hit rates and discuss their predictive value for the development of small molecule (SMOL) candidates. Purely structure‐activity relationship (SAR) based druggability ratings are compared with computational protein‐structure based druggability assessments. Secondly, we evaluate the impact of using conformational ensembles from molecular dynamics (MD) simulations instead of single static crystal structures as basis for computational druggability assessments. Based on this study, we recommend incorporating molecular dynamics routinely into the early target characterization process, especially if only a single X‐ray structure is available.

中文翻译:

制药工业环境中选定丝氨酸蛋白酶的成药性评估​​。

目标成药性评估​​是制药行业早期目标表征和选择过程中不可或缺的一部分。在这里,我们研究了来自凝血级联反应的一组五种不同的丝氨酸蛋白酶。这项研究的目的是双重的。首先,利用大量可用的内部高通量筛选 (HTS) 数据,我们分析了 HTS 命中率并讨论了它们对小分子 (SMOL) 候选药物开发的预测价值。将基于纯构效关系 (SAR) 的成药性评级与基于计算蛋白质结构的成药性评估​​进行比较。其次,我们评估了使用分子动力学 (MD) 模拟中的构象集合而不是单个静态晶体结构作为计算成药性评估​​的基础的影响。基于这项研究,
更新日期:2020-08-09
down
wechat
bug