Supplementary Materials

Supplementary Material for:

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

Dennis Plenker, Maximilian Riedel, Johannes Brägelmann, Marcel A. Dammert, Rakhee Chauhan, Phillip P. Knowles, Carina Lorenz, Marina Keul, Mike Bührmann, Oliver Pagel, Verena Tischler, Andreas H. Scheel, Daniel Schütte, Yanrui Song, Justina Stark, Florian Mrugalla, Yannic Alber, André Richters, Julian Engel, Frauke Leenders, Johannes M. Heuckmann, Jürgen Wolf, Joachim Diebold, Georg Pall, Martin Peifer, Maarten Aerts, Kris Gevaert, René P. Zahedi, Reinhard Buettner, Kevan M. Shokat, Neil Q. McDonald, Stefan M. Kast, Oliver Gautschi, Roman K. Thomas, Martin L. Sos*

*Corresponding author. Email: martin.sos{at}uni-koeln.de

Published 14 June 2017, Sci. Transl. Med. 9, eaah6144 (2017)
DOI: 10.1126/scitranslmed.aah6144

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Selective inhibition of signaling induced by rearranged RET and clinical activity in vivo.
  • Fig. S2. Induction of KIF5B-RET rearrangements in NIH-3T3 cells via CRISPR/Cas9 and S6 kinase as an off-target of AD80.
  • Fig. S3. Characterization of the activity profile of AD80.
  • Fig. S4. Delineation of the cellular targets of AD80 using ligand screens and thermal shift experiments.
  • Fig. S5. RMSD of RET and AD80 or cabozantinib over time and ALPB-optimized structures.
  • Fig. S6. Inhibitory potential of AD80 derivatives and resistance mechanisms against RET inhibition.
  • Fig. S7. Validation of PDX via fluorescent in situ hybridization (FISH) and in vivo effects induced by treatment with AD80.
  • Table S1. IC50 values of AD80, cabozantinib, and vandetanib for phospho-RET in Ba/F3 cells expressing wild type or V804M KIF5B-RET.
  • Table S2. Rates of clinical response to currently available anti-RET drugs and clinical information of patients used in retrospective analysis.
  • Table S3. GI50 values of the panel of patient-derived cell lines.
  • Table S4. Tabulated derivative melting temperatures (Tm) and differences in melting temperature (ΔTm) values.
  • Table S5. In vitro kinase assay of RETwt, RETV804M, and RETV804L mutants with different inhibitors.
  • Table S6. Experimental setup for saturated mutagenesis screening.
  • References (4366)

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