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. 2022 Apr 20;604(7907):749–756. doi: 10.1038/s41586-022-04638-9

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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. 2 — a, Chemical structure of the PKMYT1 inhibitor RP-6306. b, Dose–response of PKMYT1 catalytic activity to RP-6306 as measured with the ADP-Glo kinase assay. Data are mean ± s.d. (n = 3). c, Target engagement of RP-6306 on PKMYT1 (left) and WEE1 (right) in a NanoBRET assay reported in milliBRET units (mBU). Data are mean ± s.d. (n = 3). d, Clonogenic survival of the indicated FT282-hTERT TP53^R175H derivatives treated with RP-6306. Left, representative images of plates stained with crystal violet. Right, quantification of clonogenic survival assays. Data are mean ± s.d. (n = 3). e, f, EC₅₀ determination for growth inhibition for the parental and CCNE1-high cells in the RPE1-hTERT TP53^−/− Cas9 (RPE1) and FT282-hTERT TP53^R175H (FT282) backgrounds (e) and indicated cancer cell lines (f) treated with the indicated compounds. Growth was monitored with an Incucyte live-cell imager for up to six population doublings. Data are mean ± s.d. (n = 3). Additional data are presented in Extended Data Fig. 2g, h. In f, cell lines are also grouped according to their CCNE1 or BRCA status and the red bar indicates the mean of each grouping.

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