Extended Data Fig. 7: Cyclin A/B RxL and CDK2 Inhibitors Act via Distinct Mechanisms.
From: Targeting G1–S-checkpoint-compromised cancers with cyclin A/B RxL inhibitors
a, Immunoblot analysis of NCI-H1048 cells treated with indicated doses of Cdk2 inhibitor (PF-07104091) for 24 h. CIRc-004 (200 nM) is included as a benchmark control. b, Representative flow cytometric analysis of EdU and DAPI in NCI-H1048 cells treated with PF-07104091 at 500 nM or DMSO (vehicle) for 24 h. c, Quantification of the EdU positive 4c population after drug treatment shown in b. Data are mean +/− SD. n = 3 biological replicates. Statistical significance calculated using unpaired, two-tailed students t-test. **=p < 0.01. d, Heat map of z-scores from RNA-seq data of NCI-H1048 cells treated with the Cdk2 inhibitor (PF-07104091 at 500 nM), cyclin A/B RxL inhibitor (CIRc-004 at 200 nM), or DMSO for 24 h. Data is sorted for Log2FoldChange of Cdk2 inhibitor (replicate 1 and 2) vs. DMSO (replicate 1 and 2) showing genes with padj<0.05 which was 110 top up-regulated and 113 down-regulated genes. n = 2 biological replicates. Relevant up-regulated genes are labelled on right. e, Bar graphs showing top significantly enriched Hallmark pathways (padj<0.05) calculated using differentially expressed genes from bulk RNA-seq experiment in d comparing Cdk2 inhibitor vs. DMSO in NCI-H1048 cells.
