Freie Universität Berlin
Institute of Pharmacy
+49 30 838 53272
The Rademann lab is focused on the Medicinal Chemistry of cancer and infection using strategies of fragment-based drug discovery introduced by our group.
These strategies include fragment ligation assays, which are able to construct and detect fragment combinations with superior affinity and efficacy.
Specific inhibitors of protein tyrosine phosphatases (PTP) and protein-protein-interactions (PPI) have been discovered starting from novel and proprietary phosphotyrosine-mimetic fragments.
Molecules developed in our group have been successfully applied to the validation of proteins as drug targets, including the protein tyrosine phosphatase SHP2 and the transcription factor STAT5.
Our SHP2 inhibitor GS493 has recently shown to block efficiently the growth of KRAS-mutated pancreatic ductal carcinoma (PDAC) in mice when used in a combination with the specific kinase inhibitor Trametinib (D. Ruess et al., Nat. Med. 2018, doi.org/10.1038/s41591-018-0024-8).
We offer projects in the fragment-based discovery of anti-cancer drugs in three areas:
- inhibitors of the protein tyrosine phosphatase SHP2
- inhibitors of the transcription factor STAT5
- senolytic drugs.
We are looking for highly motivated individuals that enjoy working in a multidisciplinary and multicultural research environment ranging from synthetic medicinal chemistry to biochemistry, biophysics and molecular biology.
- E-. L. Wong, E. Nawrotzky, C. Arkona, B. G. Kim, S. Beligny, X. Wang, S. Wagner, M. Lisurek, D. Carstanjen, J. Rademann "The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation", Nature Commun. 2019, 10, 66.
- M. Jaegle, E. L. Wong, C. Tauber, E. Nawrotzky, C. Arkona, J. Rademann, “Protein-templated fragment ligations: from molecular recognition to drug discovery”, Angew. Chem. Int. Ed. 2017, 56, 7358-7378.
- S. Wagner, M. Accorsi, J. Rademann “Benzyl Mono-P-Fluorophosphonate and Benzyl Penta-P-Fluorophosphate Anions Are Physiologically Stable Phosphotyrosine Mimetics and Inhibitors of Protein Tyrosine Phosphatases”, Chem Eur. J. 2017, 23, 15387-15395.
- S. Grosskopf, C. Eckert, C. Arkona, S. Radetzki, K. Böhm, U. Heinemann, G. Wolber, J.-P. von Kries, W. Birchmeier, J. Rademann, „Selective inhibitors of the protein tyrosine phosphatase SHP2 block cellular motility and growth of cancer cells in-vitro and in-vivo”, ChemMedChem 2015, 10, 815-826.
- L. Lan, J. D. Holland, J. Qi, S. Grosskopf, J. Rademann, R. Vogel, B. Györffy, A. Wulf-Goldenberg, W. Birchmeier “Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice”, EMBO J. 2015, 34, 1493-1508.4.