Fig. 1

Identification of drugs depleting tumor-associated SAMHD1. a, b To identify small-molecule drugs capable of effectively downregulating SAMHD1 protein expression, a functional screen of 122 small-molecule drugs covering 121 cellular signaling pathways was conducted. Western blot analysis was used to evaluate their regulatory effects on SAMHD1 protein expression. a Pie chart showing the distribution of the 121 cellular pathways targeted by the 122 screened drugs. Different colors represent distinct pathway categories, with the proportional share of each color indicating the percentage of drugs corresponding to each pathway category relative to the total. The top 15 most represented pathways (by drug count) are annotated individually. b The effects of drugs on SAMHD1 expression were examined by western blot and quantified using ImageJ. STA-9090, highlighted in red, was found to be the most potent in degrading SAMHD1 protein expression level among the 122 drugs (n = 3). c SAMHD1 in THP-1 cells was knocked down via shRNA transduction. The expression level of endogenous SAMHD1 in the cells was verified by Western blot, with GAPDH used as the internal reference protein. d, e SAMHD1-knockdown or control THP-1 cells were treated with 100 nM cytarabine for 24 h, and cell apoptosis rate was detected by flow cytometry (n = 3). f, g Cytotoxicity assay of cytarabine in SAMHD1 knockdown f THP-1 and g Molm-13 cells (n = 3). h–m Kaplan–Meier plots of various cancer patients after inquartation for SAMHD1 mRNA expression levels. Hazard ratio (HR) and p values are indicated. LAML acute myeloid leukemia, BRCA breast invasive carcinoma, LGG brain lower-grade glioma, STAD stomach adenocarcinoma, THYM thymoma, UVM uveal melanoma