Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Neurology

Stroke

Arachidonate 15-lipoxygenase (ALOX15; 15-LOX)

In vitro and mouse studies suggest a new class of ALOX15 inhibitors could help treat stroke. Chemical synthesis and in vitro testing of oxazole-4-carbonitrile analogs identified a lead compound that inhibited ALOX15 with a nanomolar IC50 value. In a mouse neuron-based assay of Alox15-mediated oxidative stress, the lead compound caused a dose-dependent decrease in cell death compared with no treatment. In mouse models of ischemic stroke, i.p. injection of the lead compound two hours after ischemia decreased infarct size compared with vehicle injection. Ongoing work includes optimizing the lead compound and testing it in additional mouse models of stroke and other cerebrovascular diseases.

SciBX 7(17); doi:10.1038/scibx.2014.499
Published online May 1, 2014

Patent application filed by Massachusetts General Hospital; available for licensing

Holman, T.R. et al. J. Med. Chem.; published online March 31, 2014;
doi:10.1021/jm401915r
Contact: Klaus van Leyen, Harvard Medical School, Charlestown, Mass.
e-mail:

klaus_vanleyen@hms.harvard.edu
Contact: David J. Maloney, National Institutes of Health, Bethesda, Md.
e-mail:

maloneyd@mail.nih.gov
Contact: Theodore Russell Holman, University of California, Santa Cruz, Calif.
e-mail:

tholman@chemistry.ucsc.edu