Small molecule inhibitors of ferroptosis for therapeutic applications

This technology is a series of compounds that modulate ferroptosis for the treatment of excitotoxic and degenerative diseases.

Unmet Need: Potent and selective modulators of ferroptosis

Ferroptosis has been implicated in numerous pathologies, including Huntington’s disease, kidney disease, and traumatic brain injury. While modulation of ferroptosis is an attractive therapeutic strategy for the treatment of such conditions, existing compounds that inhibit this cell death pathway (ferrostatins) lack drug-like properties. As such, there remains a need for potent small molecule inhibitors of ferroptosis that possess enhanced molecular properties to allow for further drug development.

The Technology: Compounds that inhibit ferroptosis and ameliorate excitotoxicity

This technology describes a series of small-molecule ferroptosis modulators with enhanced drug-like properties over presently available ferrostatins. The compounds, which possess variable structures and moieties, effectively inhibit ferroptosis and reduce reactive oxygen species (ROS) in human cells. Importantly, the compounds may be administered alone or in combination with other therapeutic compounds for the treatment of degenerative diseases involving lipid peroxidation, as well as excitotoxic disorders involving oxidative cell death. The compounds and methods described by this technology may be further developed into therapeutics for the treatment or amelioration of various pathologies, including neurodegenerative diseases, stroke, and kidney disease.

Applications:

• Small-molecule drugs for neurodegenerative diseases
• Treatments for epilepsy, stroke, and traumatic brain injury
• Treatments for kidney disease, myocardial infarction, and diabetes
• Alleviation of side effects from radiotherapy and immunotherapy
• Research reagents for the study of ferroptosis

Advantages:

• Improved molecular properties over currently available compounds
• Permits substitution of diverse moieties and structures
• Demonstrated effectiveness in models of ferroptosis
• Permits co-administration with other therapeutic agents
• Applicable to numerous pathological conditions

Lead Inventor:

Brent Stockwell, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Gaschler MM, Hu F, Feng H, Linkermann A, Min W, Stockwell BR. “Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis” ACS Chem Biol. 2018 Apr 20; 13(4): 1013-1020.

• Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K, Rosenberg PA, Lo DC, Weinberg JM, Linkermann A, Stockwell BR. “Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models” J Am Chem Soc. 2014 Mar 26; 136(12): 4551-4556.

Tech Ventures Reference:

• IR CU17132

• Licensing Contact: Beth Kauderer