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. 2022 Oct 27;32(12):1105–1123. doi: 10.1038/s41422-022-00735-6

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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. 7 — a The scheme of the screening protocol for UHRF1 inhibitor. b The structural formula of UHRF1 inhibitor UF146. c The binding mode of UF146 to the G465, A463, G448 and V446-created 5mC cavity in SRA domain. d, e The SPR (d) and FRET (e) analysis were performed to examine the direct binding affinities of UF146 to the SRA domain of UHRF1 (n = 3). f The cellular viability of human CD34⁺ HSPCs, Kasumi-1 and THP-1 cells treated with UF146 or the vehicle was examined by MTT assay (n = 3). g The cellular viability of AML cells (Kasumi-1, SKNO-1, HL60, NB4, OCI-AML3, THP-1, NOMO-1, MOLM-13, MV4-11 and SKM-1 cells) treated with UF146 or the vehicle control for 48 h. h, i The representative flow cytometry analysis profiles (h) and quantification (i) analysis of the early apoptosis and late apoptosis in the primary AML patient cells 24 h after the treatment of UF146 or the vehicle control (n = 3). j The Wright’s staining of the primary AML cells treated with the vehicle or UF146. k The number of colonies generated from AE9a- or MLL-AF9-driven LICs treated with UF146 or the vehicle (n = 3). l The number of colonies generated from the primary AML patient cells treated with UF146 or the vehicle (n = 3). m The cluster dendrogram analysis of AML cells treated with UF146 and AML cells with knockdown of UHRF1. n The RNA-seq and GSEA analysis of the AML cells treated with UF146 or the vehicle. o, p The DNA methylation levels of MXD4 in UF146- or the vehicle-treated Kasumi-1 (o) and THP-1 (p) cells were analyzed by the bisulfite sequencing (n = 3). q Western blotting analysis of UHRF1/MXD4/SAP30 in AML cells 24 h after UF146 treatment. Statistical analyses were performed using Student’s unpaired t-test for i, k, l, o and p. *P < 0.05, **P < 0.01, ***P < 0.001.