Selective 12-Human Lipoxygenase Inhibitors for the Treatment of Diabetes and Clotting


This invention discloses small molecule inhibitors of human 12-lipoxygenase (12-hLO). 12-lipoxygenase expression, activation, and lipid metabolites have been implicated in type 1 and type 2 diabetes, cardiovascular disease, hypertension, Alzheimer’s, and Parkinson’s disease. The development of 12-hLO inhibitors may be a potent intracellular approach to decreasing the ability of platelets to form large clots in response to vessel injury or activation of the coagulation pathway. Thus, 12-hLO inhibition has the potential to attenuate platelet-mediated clot formation caused by diabetes and/or cardiovascular disease and significantly decrease the occurrence of myocardial infarction and death. Moreover, Type 1 and Type 2 diabetes are serious disorders that can lead to major complications and reduced lifespan. An unmet medical need is to identify new ways to protect beta cells in these metabolic disorders. A selective 12-hLO inhibitor could provide a new therapeutic approach to prevent or treat either form of diabetes.

Potential Commercial Applications: Competitive Advantages:
  • Therapeutic developments (blood clots; Type 1 and Type 2 diabetes, cardiovascular disease, and neurodegenerative diseases)
  • Inflammatory responses
 
  • Small molecule (series of analogs can be derived in search of improved performances and/or different functions)
  • Selective inhibitor of human 12-lipoxygenase


Development Stage:
Pre-clinical

Inventors:

David Maloney (NCATS)  ➽ more inventions...

Theodore Holman

Jerry Nadler

Michael Holinstat

Anton Simeonov (NCATS)  ➽ more inventions...

Ajit Jadhav (NCATS)  ➽ more inventions...


Intellectual Property:
US Application No. 61/345,708
PCT Application No. PCT/US11/37000
US Application No. 13/698,340

Publications:
Bleich D, et al. PMID 10330425
Yeung J, Holinstat M. PMID 21838667
Ma K, et al. PMID 20089617
Yeung J, et al. PMID 22155783
Kenyon V, et al. PMID 21739938
Nunemaker CS, et al. PMID 18780776
Chakrabarti SK, et al. PMID 19521344

Licensing Contact:
Suryanarayana Vepa, Ph.D.
Email: sury.vepa@nih.gov
Phone: 301-217-9197

OTT Reference No: E-134-2010/0
Updated: Nov 18, 2015