Jadhav, Ajit (NCATS)
Simeonov, Anton (NCATS)
Yasgar, Adam (NCATS)
Luci, Diane (NCATS)
Holinstat, Michael (Thomas Jefferson University)
Holman, Theodore (University of California, Santa Cruz)
Nadler, Jerry (Eastern Virginia Medical School)
Taylor-Fishwick, David (Eastern Virginia Medical School)
This technology includes the discovery and use of novel selective 12-LO (lipoxygenase) inhibitors, 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives, for attenuating large clots and for the treatment of Type 1/2 diabetes. A 12-LO inhibitor could be a potent intracellular approach to block platelets from forming large clots in response to vessel injury or activation of the coagulation pathway, either due to diabetes and/or cardiovascular disease. Blocking clot formation can significantly decrease the occurrence of myocardial infarction and death.
With further development, the small molecules covered by this technology have the potential to be a therapeutic, but minimally can serve as a starting point to further validate 12-LO as a therapeutic target.
The small molecules covered in this patent represent novel 12-LO inhibitors which are soluble, have favorable ADME properties, and good in vivo PK. There are no current commercially available 12-LO inhibitors, so these agents have the possibility of being first in class.