PDF(Pubmed)
Abstract：
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.
摘要：
肝细胞癌（HCC）是癌症相关死亡的主要原因。FGFR4与HCC进展有关，使其成为有希望的治疗目标。我们介绍了一种通过向普通弹头单元顺序添加片段来鉴定新型FGFR4抑制剂的方法。这种策略导致发现了一种有效的抑制剂，4c,在FGFR家族成员中具有33nM的IC50和高选择性。尽管需要进一步优化，我们的方法证明了发现有效的FGFR4抑制剂用于HCC治疗的潜力，并提供了从小碎片中获得命中化合物的有用方法。
