Ginex Tiziana, Madruga Enrique, Martinez Ana, Gil Carmen
Centro de Investigaciones Biológicas "Margarita Salas" (CIB-CSIC), Madrid, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Front Pharmacol. 2023 Aug 11;14:1244317. doi: 10.3389/fphar.2023.1244317. eCollection 2023.
Chemical libraries have become of utmost importance to boost drug discovery processes. It is widely accepted that the quality of a chemical library depends, among others, on its availability and chemical diversity which help in rising the chances of finding good hits. In this regard, our group has developed a source for useful chemicals named Medicinal and Biological Chemistry (MBC) library. It originates from more than 30 years of experience in drug design and discovery of our research group and has successfully provided effective hits for neurological, neurodegenerative and infectious diseases. Moreover, in the last years, the European research infrastructure for chemical biology EU-OPENSCREEN has generated the European Chemical Biology library (ECBL) to be used as a source of hits for drug discovery. Here we present and discuss the updated version of the MBC library (MBC v.2022), enriched with new scaffolds and containing more than 2,500 compounds together with ECBL that collects about 100,000 small molecules. To properly address the improved potentialities of the new version of our MBC library in drug discovery, up to 44 among physicochemical and pharmaceutical properties have been calculated and compared with those of other well-known publicly available libraries. For comparison, we have used ZINC20, DrugBank, ChEMBL library, ECBL and NuBBE along with an approved drug library. Final results allowed to confirm the competitive chemical space covered by MBC v.2022 and ECBL together with suitable drug-like properties. In all, we can affirm that these two libraries represent an interesting source of new hits for drug discovery.
化学文库对于推动药物发现过程已变得至关重要。人们普遍认为,化学文库的质量尤其取决于其可用性和化学多样性,这有助于提高找到优质活性化合物的几率。在这方面,我们团队开发了一个名为药用与生物化学(MBC)文库的有用化学品来源。它源自我们研究团队30多年的药物设计和发现经验,并已成功为神经、神经退行性和传染性疾病提供了有效的活性化合物。此外,在过去几年中,欧洲化学生物学研究基础设施EU-OPENSCREEN生成了欧洲化学生物学文库(ECBL),用作药物发现的活性化合物来源。在此,我们展示并讨论MBC文库的更新版本(MBC v.2022),它富含新的骨架,包含2500多种化合物,同时还有收集了约100000个小分子的ECBL。为了恰当地评估我们新版本的MBC文库在药物发现方面的改进潜力,我们计算了多达44种物理化学和药物性质,并与其他知名的公开可用文库进行了比较。为了进行比较,我们使用了ZINC20、DrugBank、ChEMBL文库、ECBL和NuBBE以及一个已批准药物文库。最终结果证实了MBC v.2022和ECBL所覆盖的具有竞争力的化学空间以及合适的类药性质。总之,我们可以肯定这两个文库是药物发现新活性化合物的一个有趣来源。