Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico; PECEM, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico.
Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico.
Drug Discov Today. 2018 Jan;23(1):141-150. doi: 10.1016/j.drudis.2017.10.006. Epub 2017 Oct 14.
As the number of compounds tested against epigenetic targets grows, exploration of the possible associations in chemical space among these targets could lead to the identification of new drugs or new designs of epipolypharmacological molecules. Thus, here we review compound-epitarget associations of public databases. Specifically, we explore the structure-multitarget activity relationships and diversity of over 7000 compounds tested against 52 epigenetic-related targets. We found that, whereas inhibitors of histone deacetylases and other epigenetic targets are clustered in the chemical space, the chemical space of inhibitors of different DNA methyltransferases (DNMTs) did not overlap, indicating DNMT selectivity. These and other compound-epitarget relationships discussed here could be useful for both drug repurposing and the rational design of epipolypharmacological compounds.
随着针对表观遗传靶点的化合物数量的增加，对这些靶点在化学空间中可能存在的关联的探索可能会导致新药物或新型表观多效性分子的设计。因此，在这里我们回顾了公共数据库中的化合物-靶标关联。具体来说，我们探索了超过 7000 种化合物针对 52 个表观遗传相关靶点的结构-多靶活性关系和多样性。我们发现，组蛋白去乙酰化酶和其他表观遗传靶点的抑制剂在化学空间中聚集，而不同 DNA 甲基转移酶（DNMT）抑制剂的化学空间没有重叠，表明 DNMT 具有选择性。这里讨论的这些化合物-靶标关系对于药物再利用和合理设计表观多效性化合物都可能是有用的。
