This technology includes the identification and use of 12/15-lipoxygenase (LOX) inhibitors, including ML351 and related analogs, for post-stroke treatment. The 12/15-LOX directly oxidizes lipid membranes leading to their direct attack. After a stroke, the activity of 12/15-LOX is upregulated and is thought to contribute to increased neuronal loss and blood-brain barrier leakage. A high-throughput screen was undertaken to find inhibitors, which were then subjected to medical chemistry optimization.
Identification of LOX inhibitors has been difficult because many of the inhibitors found have been antioxidants with low selectivity and low potency. The identified ML351-based compounds have been used in human and mouse studies and found to be potent and selective LOX inhibitors.