Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors

Author:

Plenker Dennis12ORCID,Riedel Maximilian12ORCID,Brägelmann Johannes12ORCID,Dammert Marcel A.12,Chauhan Rakhee3,Knowles Phillip P.3,Lorenz Carina12,Keul Marina4ORCID,Bührmann Mike4,Pagel Oliver5ORCID,Tischler Verena2,Scheel Andreas H.6ORCID,Schütte Daniel2,Song Yanrui7ORCID,Stark Justina4ORCID,Mrugalla Florian4,Alber Yannic4,Richters André4,Engel Julian4,Leenders Frauke8,Heuckmann Johannes M.8ORCID,Wolf Jürgen9,Diebold Joachim10,Pall Georg11,Peifer Martin2,Aerts Maarten1213ORCID,Gevaert Kris1213,Zahedi René P.5,Buettner Reinhard6,Shokat Kevan M.14,McDonald Neil Q.315ORCID,Kast Stefan M.4,Gautschi Oliver10,Thomas Roman K.2916,Sos Martin L.12ORCID

Affiliation:

1. Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.

2. Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.

3. Structural Biology Laboratory, Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK.

4. Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.

5. Leibniz-Institut für Analytische Wissenschaften–ISAS–e.V., Dortmund, Germany.

6. Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.

7. Crown BioScience, Inc., 3375 Scott Blvd, Suite 108, Santa Clara, CA 95054, USA.

8. NEO New Oncology GmbH, 51105 Cologne, Germany.

9. Department of Internal Medicine, Center for Integrated Oncology Köln Bonn, University Hospital Cologne, Cologne, 50931 Cologne, Germany.

10. Cancer Center, Lucerne Cantonal Hospital, 6000 Lucerne, Switzerland.

11. Department of Internal Medicine 5, University Hospital Innsbruck, Haematology/Oncology, Anichstraße 35, 6020 Innsbruck, Austria.

12. VIB-UGent Center for Medical Biotechnology, VIB, B-9000 Ghent, Belgium.

13. Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.

14. Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

15. Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, Malet Street, London WC1E 7HX, UK.

16. German Cancer Consortium (DKTK), partner site Heidelberg, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

An examination of the activity profiles of RET inhibitors suggests potential treatment for RET -rearranged cancers.

Funder

Howard Hughes Medical Institute

Senatsverwaltung für Bildung, Jugend und Wissenschaft, Berlin

Deutsche Forschungsgemeinschaft

EFREinitiative

PerMed.NRW

PerMed NRW

Bundesministerium für Bildung und Forschung

EMBO

EFRE initiative

EFRE-initiative

Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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