Improving 15-LOX-2 small molecule inhibitors through medicinal chemistry and structure-guided design

National Center For Advancing Translational Sciences

Investigators

Abstract

This project aims to build on previous screening work by developing selective and potent 15-LOX-2 inhibitors, specifically ones capable of disrupting the 15-LOX-2/PEBP1 protein-protein complex and modulate ferroptosis both in in vitro and in vivo models. During this period, the collaborative team worked to outline a research plan to accomplish the stated project goals. Initial work was done to design and develop potential cell-based assays, and medicinal chemistry strategies were discussed for the current 15-LOX-2 inhibitor leads. The project team has identified a small molecule that inhibits ferroptosis, and is currently pursuing analogs of the chemotype.