Department of Life Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 103, 41125 Modena, Italy.
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Int J Mol Sci. 2023 Feb 5;24(4):3135. doi: 10.3390/ijms24043135.
Prostate cancer (PC) is one of the most common types of cancer in males. Although early stages of PC are generally associated with favorable outcomes, advanced phases of the disease present a significantly poorer prognosis. Moreover, currently available therapeutic options for the treatment of PC are still limited, being mainly focused on androgen deprivation therapies and being characterized by low efficacy in patients. As a consequence, there is a pressing need to identify alternative and more effective therapeutics. In this study, we performed large-scale 2D and 3D similarity analyses between compounds reported in the DrugBank database and ChEMBL molecules with reported anti-proliferative activity on various PC cell lines. The analyses included also the identification of biological targets of ligands with potent activity on PC cells, as well as investigations on the activity annotations and clinical data associated with the more relevant compounds emerging from the ligand-based similarity results. The results led to the prioritization of a set of drugs and/or clinically tested candidates potentially useful in drug repurposing against PC.
前列腺癌（PC）是男性最常见的癌症类型之一。尽管 PC 的早期阶段通常与良好的结果相关，但该疾病的晚期阶段预后明显较差。此外，目前用于治疗 PC 的治疗选择仍然有限，主要集中在雄激素剥夺疗法上，并且在患者中的疗效较低。因此，迫切需要确定替代的、更有效的治疗方法。在这项研究中，我们对 DrugBank 数据库中报道的化合物和具有报道的抗增殖活性的 ChEMBL 分子进行了大规模的 2D 和 3D 相似性分析，这些化合物在各种 PC 细胞系上具有活性。分析还包括鉴定对 PC 细胞具有强大活性的配体的生物靶标，以及对与基于配体相似性结果中出现的更相关化合物相关的活性注释和临床数据的研究。这些结果导致了一组药物和/或临床测试候选药物的优先级确定，这些药物可能在针对 PC 的药物再利用中有用。
