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Therapeutic Inhibition of System xC- by Sorafenib

Summary

System xC- is a cysteine/glutamate antiporter whose inhibition induces ferroptotic cell death. Therapeutic inhibition of system xC- for targeted cell death in certain cancers has previously been stymied by the low potency and poor pharmacokinetics of known inhibitors. This technology identifies the small molecule sorafenib, an FDA approved drug, and a set of analogs as potent inhibitors of system xC-. Development and application of these inhibitors could lead to treatments for diseases involving system xC- dysfunction, including many cancers and neurological conditions.

Technology Benefits

Sorafenib has been FDA approved for other indications, demonstrating good pharmacokinetic properties and bioavailability.A suite of potent analogs of sorafenib can expedite the development of a system xC- inhibitor by reducing time spent on lead optimization.A potent system xC- inhibitor is applicable to many clinical areas, potentially creating a large market for clinical system xC- inhibitorsPatent Information:Patent Pending (WO/2015/051149)Tech Ventures Reference: IR CU13331

Technology Application

Development of sorafenib analogs that are potent inhibitors of system xC-Development of sorafenib and its analogs as a therapeutic for neural diseases related to system xC- dysfunction, such as Parkinson's disease, schizophrenia, and depressionDevelopment of sorafenib and its analogs as a therapeutic for cancersUse of sorafenib and its analogs for research on system xC-

Detailed Technology Description

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*Abstract

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*Inquiry

Beth KaudererColumbia Technology VenturesTel: (212) 854-8444Email: TechTransfer@columbia.edu

*IR

CU13331

*Principal Investigator

*Publications

Dixon, S.J., Patel, D.N., Welsch, M., Skouta, R., Lee, E.D., Hayano, M., Thomas, A.G., Gleason, C.E., Tatonetti, N.P., Slusher, B.S., Stockwell, B.R. "Pharmacological inhibition of cystinepglutamate exchange induces endoplasmic reticulum stress and ferroptosis" eLife. 2014 May 20; e02523.

Country/Region

USA