Figure 6 from Efficacy of CBP/p300 Dual Inhibitors against Derepression of KREMEN2 in cBAF-Deficient Cancers
Authors: Sasaki Mariko , Kato Daiki , Yoshida Hiroshi , Shimizu Takafumi , Ogiwara Hideaki 
Published: January 2025

<p>A CBP/p300 dual inhibitor suppresses the growth of tumor xenografts derived from SMARCA4/SMARCA2-deficient cells and SS18–SSX fusion cells. <b>A,</b> Volume of tumor xenografts derived from SMARCA4/SMARCA2-deficient DMS114 cell lines and harvested from mice treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 5 biologically independent mice per group); +CP-C27 (<i>n</i> = 6 biologically independent mice per group). <b>B,</b> Volume of tumor xenografts derived from SS18–SSX fusion Fuji cell lines and harvested from mice treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 8 biologically independent mice per group); +CP-C27 (<i>n</i> = 8 biologically independent mice per group). <b>C,</b> Weight of tumor xenografts derived from SMARCA4/SMARCA2-deficient DMS114 cell lines and harvested from mice treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 5 biologically independent mice per group); +CP-C27 (<i>n</i> = 6 biologically independent mice per group). <b>D,</b> Weight of tumor xenografts derived from SS18–SSX fusion Fuji cell lines and harvested from mice treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 8 biologically independent mice per group); +CP-C27 (<i>n</i> = 8 biologically independent mice per group). <b>E,</b> Body weight of mice engrafted with SMARCA4/SMARCA2-deficient DMS114 cell lines and treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 5 biologically independent mice per group); +CP-C27 (<i>n</i> = 6 biologically independent mice per group). <b>F,</b> Body weight of mice engrafted SS18–SSX fusion Fuji cell lines and treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 8 biologically independent mice per group); +CP-C27 (<i>n</i> = 8 biologically independent mice per group). <b>G,</b> Expression of <i>KREMEN2</i> mRNA (relative to the average of expression levels in −CP-C27 tumors) in xenografts derived from SMARCA4/SMARCA2-deficient DMS114 cell lines isolated from mice treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 4 biologically independent mice per group); +CP-C27 (<i>n</i> = 5 biologically independent mice per group). <b>H,</b> Expression of <i>KREMEN2</i> mRNA (relative to the average of expression levels in −CP-C27 tumors) in xenografts derived from SS18–SSX fusion Fuji cell lines isolated from mice treated once daily with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 5 biologically independent mice per group); +CP-C27 (<i>n</i> = 5 biologically independent mice per group). <b>I,</b> Representative immunohistochemical staining of cleaved PARP and cleaved caspase-3 in xenografts derived from SMARCA4/SMARCA2-deficient DMS114 cell lines and isolated from mice treated once daily for 20 days with 30 mg/kg CP-C27: Scale bar, 100 μm. <b>J</b> and <b>K,</b> Percentage of cells positive for cleaved caspase-3 (<b>J</b>) and cleaved PARP (<b>K</b>) in xenografts derived from SMARCA4/SMARCA2-deficient DMS114 cell lines and isolated from mice treated once daily for 20 days with 30 mg/kg CP-C27. Data are presented as the mean ± SEM. −CP-C27 (<i>n</i> = 5 biologically independent mice per group); +CP-C27 (<i>n</i> = 5 biologically independent mice per group). For all experiments, <i>P</i> values were determined by an unpaired two-tailed Student <i>t</i> test. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001. H&E, hematoxylin and eosin.</p>