Lipoxygenases play a central role in the biology of stroke, cancer, and metabolic diseases. We translate deep mechanistic discoveries into innovative, IND-ready therapies.
Our mechanistic investigations of LOX catalysis have helped us determine that many LOX isozymes have allosteric regulation sites. The allosteric site is critical to the regulation of lipoxygenase activity and is also used as an alternative site for inhibition. It is thus the target for a novel class of lipoxygenase inhibitors. We have probed the binding constraints of the allosteric site, which helps us to rationally design allosteric inhibitors.
We currently have discovered over 50 unique lipoxygenase inhibitors through screening a marine natural products library and the NIH Chemical Genomics Center (NCGC) inhibitor library. The marine natural products library is one of the worlds largest and offers a unique source of novel chemical structures unavailable through standard synthetic or combinatorial methods. The NCGC library has over 400,000 compounds and was screened with advanced robotic methods in 8 hours. We currently have hundreds of hits from both libraries and are investigating the most drug-like compounds with biochemical and spectroscopic methods.
