Nature Communications (Sep 2020)

Inhibitors of BRAF dimers using an allosteric site

  • Xiomaris M. Cotto-Rios,
  • Bogos Agianian,
  • Nadege Gitego,
  • Emmanouil Zacharioudakis,
  • Orsi Giricz,
  • Yang Wu,
  • Yiyu Zou,
  • Amit Verma,
  • Poulikos I. Poulikakos,
  • Evripidis Gavathiotis

DOI
https://doi.org/10.1038/s41467-020-18123-2
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 16

Abstract

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FDA-approved RAF inhibitors poorly inhibit BRAF dimers, which limits their clinical efficacy in tumors expressing BRAFV600E mutant monomers. Here the authors identify FDA-approved Ponatinib as an effective inhibitor of BRAF monomers and dimers and designed PHI1, an inhibitor with a unique mode of action and selectivity for oncogenic BRAF dimers.