Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach.

ABSTRACT: The human 15-lipoxygenase-2 (h15-LOX-2) catalyzes mainly the regio- and stereospecific oxygenation of arachidonate to its corresponding hydroperoxide (15(S)-HpETE). h15-LOX-2 is implicated in the biosynthesis of inflammatory lipid mediators and plays a role in the development of atherosclerotic plaques, but it is still underexploited as a drug target. Here, to search for novel h15-LOX-2 inhibitors, we used a virtual screening (VS) approach consisting of shape-based matching, two-dimensional (2D) structural "dissimilarity", docking, and visual inspection filters, which were applied to a "curated" ZINC database (∼8 × 10⁶ compounds). The VS was experimentally validated, and six micromolar-range inhibitors were identified among 13 tested compounds (46.2%). The K_i

SUBMITTER: Viviani LG 

PROVIDER: S-EPMC11726667 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature