The process of blocking 5-lipoxygenase (5-LOX) catalyzed leukotriene biosynthesis has been recognized for the past few decades as a promising therapeutic strategy for acute inflammatory, allergic, and respiratory diseases. Due to the toxicity effect of FDA approved 5-LOX inhibitor zileuton, novel 5-LOX inhibitors have been sought by the scientific community. As a result, a significant and relevant amount of information on the structure-activity of 5-LOX inhibitors has been released and stored in public databases. In this study, we aimed at the comprehensive cheminformatic characterization of the diversity and complexity of the chemical space of 5-LOX inhibitors and its activating protein FLAP inhibitors by comparing it with the Approved drug space and virtual LOX library. The visual representation of the property space indicates some compounds in the 5-LOX inhibitors space broaden the traditional medicinal space. The structural diversity of the databases is computed using complementary approaches, including Physicochemical Property (PCP) descriptors, molecular fingerprints, and molecular scaffold. With the apparent exception of approved drugs, the 5-LOX dataset shows more diversity compared to FLAP and LOX virtual library set. This study was able to identify the underlying patterns in the chemical and pharmacological properties space that were decisive for the drug discovery and development of 5-LOX inhibitors.

在过去的几十年中，阻断5-脂氧合酶（5-LOX）催化的白三烯生物合成的过程已被认为是急性炎症，过敏和呼吸系统疾病的一种有前途的治疗策略。由于FDA批准的5-LOX抑制剂齐留通的毒性作用，科学界一直在寻找新型的5-LOX抑制剂。结果，关于5-LOX抑制剂的结构活性的大量和相关信息已经发布并存储在公共数据库中。在这项研究中，我们旨在通过与批准的药物空间和虚拟LOX库进行比较，对5-LOX抑制剂及其活化蛋白FLAP抑制剂的化学空间的多样性和复杂性进行全面的化学信息学表征。属性空间的可视化表示5-LOX抑制剂空间中的某些化合物拓宽了传统医学空间。数据库的结构多样性是使用互补方法计算的，其中包括物理化学性质（PCP）描述符，分子指纹和分子支架。与FLAP和LOX虚拟文库集相比，除获批药物外，5-LOX数据集显示出更多的多样性。这项研究能够确定化学和药理特性空间中的潜在模式，这些模式对于5-LOX抑制剂的发现和开发具有决定性作用。分子指纹和分子支架。与FLAP和LOX虚拟文库集相比，除获批药物外，5-LOX数据集显示出更多的多样性。这项研究能够确定化学和药理特性空间中的潜在模式，这些模式对于5-LOX抑制剂的发现和开发具有决定性作用。分子指纹和分子支架。与FLAP和LOX虚拟文库集相比，除获批药物外，5-LOX数据集显示出更多的多样性。这项研究能够确定化学和药理特性空间中的潜在模式，这些模式对于5-LOX抑制剂的发现和开发具有决定性作用。