Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven’t been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC₅₀ of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC₅₀ of 9 μM in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition.

组蛋白脱乙酰基酶（HDAC）和成纤维细胞生长因子受体（FGFR）都是癌症治疗的重要靶标。尽管将双重HDAC药效基团与酪氨酸激酶抑制剂（TKIs）结合已取得了成功的进展，但尚未报道双重HDAC / FGFR1抑制剂。在这里，我们设计了一系列带有1 H-吲哚-3-胺和苯并异羟肟酸支架的杂种，并采用了支架跳跃和分子杂交策略。其中，化合物7j对HDAC6的抑制作用最强，IC ₅₀为34 nM，对人乳腺癌细胞系MCF-7的抑制作用最强，IC ₅₀为9μM 。。同时，该化合物还表现出中等的FGFR1抑制活性。这项研究为进一步探索双重HDAC / FGFR1抑制作用提供了新的工具化合物。