A site-moiety map and virtual screening approach for discovery of novel 5-LOX inhibitors

Kai Cheng Hsu, Wei Chun HuangFu, Tony Eight Lin, Min Wu Chao, Tzu Ying Sung, Yi Ying Chen, Shiow Lin Pan, Jih Chin Lee, Shey Cherng Tzou, Chung Ming Sun, Jinn Moon Yang

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The immune system works in conjunction with inflammation. Excessive inflammation underlies various human diseases, such as asthma, diabetes and heart disease. Previous studies found that 5-lipoxygenase (5-LOX) plays a crucial role in metabolizing arachidonic acid into inflammatory mediators and is a potential therapeutic target. In this study, we performed an in silico approach to establish a site-moiety map (SiMMap) to screen for new 5-LOX inhibitors. The map is composed of several anchors that contain key residues, moiety preferences, and their interaction types (i.e., electrostatic (E), hydrogen-bonding (H), and van der Waals (V) interactions) within the catalytic site. In total, we identified one EH, one H, and five V anchors, within the 5-LOX catalytic site. Based on the SiMMap, three 5-LOX inhibitors (YS1, YS2, and YS3) were identified. An enzyme-based assay validated inhibitory activity of YS1, YS2, and YS3 against 5-LOX with an IC50 value of 2.7, 4.2, and 5.3 μM, respectively. All three inhibitors significantly decrease LPS-induced TNF-α and IL-6 production, which suggests its potential use an anti-inflammatory agent. In addition, the identified 5-LOX inhibitors contain a novel scaffold. The discovery of these inhibitors presents an opportunity for designing specific anti-inflammatory drugs.

Original languageEnglish
Article number10510
Pages (from-to)10510
JournalScientific Reports
Issue number1
Publication statusPublished - Jun 29 2020

ASJC Scopus subject areas

  • General


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