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Edited by Mariano Barbacid, Spanish National Cancer Research Centre, Madrid, Spain, and approved December 24, 2018 (received for review July 27, 2018)
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History:
- Published in issue February 12, 2019.
- Published first January 25, 2019.
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- Previous version (January 25, 2019 - 09:42).
- You are viewing the most recent version of this article.
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Copyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Author Information
- Roman C. Hilliga,1,
- Brice Sautiera,2,
- Jens Schroedera,
- Dieter Moosmayera,
- André Hilpmanna,
- Christian M. Stegmanna,
- Nicolas D. Werbecka,
- Hans Briema,
- Ulf Boemera,
- Joerg Weiskea,
- Volker Badocka,
- Julia Mastouria,
- Kirstin Petersena,
- Gerhard Siemeistera,
- Jan D. Kahmannb,
- Dennis Wegenerb,
- Niels Böhnkea,
- Knut Eisa,
- Keith Grahama,
- Lars Wortmanna,
- Franz von Nussbauma, and
- Benjamin Badera,1
- aResearch and Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany;
- bDrug Discovery Services, Evotec AG, 22419 Hamburg, Germany
Edited by Mariano Barbacid, Spanish National Cancer Research Centre, Madrid, Spain, and approved December 24, 2018 (received for review July 27, 2018)
Footnotes
- ↵1To whom correspondence may be addressed. Email: roman.hillig{at}bayer.com or benjamin.bader{at}bayer.com.
↵2Present address: Medicinal and Synthetic Chemistry, Evotec SAS, 31036 Toulouse Cedex, France.
Author contributions: R.C.H., B.S., J.S., D.M., A.H., C.M.S., N.D.W., H.B., K.P., G.S., J.D.K., D.W., N.B., K.E., K.G., L.W., F.v.N., and B.B. designed research; R.C.H., B.S., A.H., H.B., J.M., J.D.K., and D.W. performed research; R.C.H., B.S., J.S., D.M., A.H., C.M.S., N.D.W., H.B., U.B., J.W., V.B., J.M., K.P., G.S., J.D.K., D.W., N.B., K.E., K.G., L.W., and B.B. analyzed data; and R.C.H., B.S., J.S., L.W., and B.B. wrote the paper.
Conflict of interest statement: R.C.H. B.S., J.S., D.M., A.H., C.M.S., N.D.W., H.B., U.B., J.W., V.B., J.M., K.P., G.S., N.B., K.E., K.G., L.W., F.v.N., and B.B. are or have been employees and stockholders of Bayer AG. J.D.K. and D.W. are employees of Evotec AG. R.C.H., B.S., J.S., D.M., H.B., K.P., N.B., K.E., L.W., F.v.N., and B.B. are coauthors of a patent application.
This article is a PNAS Direct Submission.
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.wwpdb.org [PDB ID codes 5OVD, 5OVE, 5OVF, 5OVG, 5OVH, and 5OVI (SOS1 complexes); 6EIE (SOS2); and 6EPL, 6EPM, 6EPN, 6EPO, and 6EPP (KRAS–SOS1 complexes)].
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1812963116/-/DCSupplemental.
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Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction
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