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. 2022 Mar 21;18(6):596–604. doi: 10.1038/s41589-022-00985-w

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Chemical structures of AMG510 (1), MRTX849 (4), MRTX1257 (5) and MRTX-EX185 (6). b, Summary of the effects of SII-P binders on ¹H−¹⁵N HSQC NMR spectra of RAS proteins. c, Examples of CSPs of GDP-loaded KRAS in the presence of MRTX849 and comparison of irreversible binding to KRAS(G12C) and reversible binding to KRAS(G12D). Spectra recorded at pH 7.4 and 298 K with 100 µM U-¹⁵N protein and 200 µM ligand.