Heparanase is a validated target in cancer therapy and a potential target for several inflammatory pathologies. A ligand-based virtual screening of commercial libraries was performed to expand the chemical space of small-molecule inhibitors. The screening was based on similarity with known inhibitors and was performed in several runs, starting from literature compounds and progressing through newly discovered inhibitors. Among the fifty-five tested compounds, nineteen had IC₅₀ values lower than 5 µM and some showed remarkable potencies. Importantly, tere- and isophthalamides derivatives belong to new structural classes of heparanase inhibitors and some of them showed enzyme affinities (61 and 63, IC₅₀ = 0.32 and 0.12 µM, respectively) similar to those of the most potent small-molecule inhibitors reported so far. Docking studies provided a comprehensive binding hypothesis shared by compounds with significant structural diversity. The most potent inhibitors reduced cell invasiveness and inhibited the expression of proangiogenic factors in tumour cell lines.

乙酰肝素酶在癌症治疗中是经过验证的靶标，并且是多种炎症病理的潜在靶标。对商业库进行基于配体的虚拟筛选，以扩展小分子抑制剂的化学空间。筛选是基于与已知抑制剂的相似性，并从文献化合物开始逐步进行新发现的抑制剂，并进行了数次运行。在55种测试化合物中，有19种的IC ₅₀值低于5 µM，有些显示出显着的效能。重要的是，对苯二甲酰胺和间苯二甲酰胺衍生物属于乙酰肝素酶抑制剂的新结构类别，其中一些具有酶亲和力（61和63，IC ₅₀分别等于0.32和0.12 µM），与迄今为止报道的最有效的小分子抑制剂相似。对接研究提供了具有显着结构多样性的化合物共有的全面结合假说。最有效的抑制剂可降低细胞侵袭性并抑制肿瘤细胞系中促血管生成因子的表达。