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Drug Discovery and Development

Proneth Lab

About our Research

"Ferroptotic cell death is thought to be the root cause of many degenerative diseases while ferroptosis suppression has been put forward as Achilles’ heel for therapy-resistant tumors. Ferroptosis modulators have a vast potential for the treatment of as-yet-incurable diseases."

The development of strategies for the inhibition or induction of ferroptosis holds great promise to yield new treatment modalities for a myriad of diseases marked by early cell loss or uncontrolled proliferation. The drug discovery and development group at MCD is working on all stages of the drug discovery process ranging from assay development, high-throughput screening, optimization of hit and lead candidates using medicinal chemistry and ADME/DMPK assays to non-clinical development studies in order to advance ferroptosis modulating agents into the clinic. Currently, we are focusing on developing ferroptosis inhibitors (i.e. liproxstatins) for the treatment of organ injury and transplantation related conditions as well as neurodegeneration. In addition, we have discovered several classes of ferroptosis inducers that will be tested in a series of tumor models for their potential to eradicate treatment-resistant cancer entities. Lastly, in order to unambiguously demonstrate ferroptosis engagement in affected tissues and to monitor response to treatment with ferroptosis modulating drugs, we aim to develop novel pharmacodynamic markers and biomarkers using newly established in vivo ferroptosis models and state-of-the-art (epi)lipidomic studies.

Scientists at Drug Discovery and Development

Dr. Bettina Proneth

Deputy Director

Highlight Publications

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2022 Scientific Article in Nature

Mishima, E. ; Ito, J. ; Wu, Z. ; Nakamura, T. ; Wahida, A. ; Doll, S. ; Tonnus, W. ; Nepachalovich, P. ; Eggenhofer, E. ; Aldrovandi, M. ; Henkelmann, B. ; Yamada, K.i. ; Wanninger, J. ; Zilka, O. ; Sato, E. ; Feederle, R. ; Hass, D, ; Maida, A. ; Mourao, A. ; Linkermann, A. ; Geissler, E.K. ; Nakagawa, K. ; Abe, T. ; Fedorova, M. ; Proneth, B. ; Pratt, D.A. ; Conrad, M.

A non-canonical vitamin K cycle is a potent ferroptosis suppressor.

2021 Scientific Article in Nature Communications

Tonnus, W. ; Meyer, C. ; Steinebach, C. ; Belavgeni, A. ; von Mässenhausen, A. ; Gonzalez, N.Z. ; Maremonti, F. ; Gembardt, F. ; Himmerkus, N. ; Latk, M. ; Locke, S. ; Marschner, J.A. ; Li, W. ; Short, S.C. ; Doll, S. ; Ingold, I. ; Proneth, B. ; Daniel, C. ; Kabgani, N. ; Kramann, R. ; Motika, S. ; Hergenrother, P.J. ; Bornstein, S.R. ; Hugo, C. ; Becker, J.U. ; Amann, K. ; Anders, H.J. ; Kreisel, D. ; Pratt, D.A. ; Gütschow, M. ; Conrad, M. ; Linkermann, A.

Dysfunction of the key ferroptosis-surveilling systems hypersensitizes mice to tubular necrosis during acute kidney injury.

Contact

Dr. Bettina Proneth

Deputy Director