Identification of potential NUDT5 inhibitors from marine bacterial natural compounds via molecular dynamics and free energy landscape analysis.

NUDIX hydrolase 5 (NUDT5) is an enzyme involved in the hydrolysis of nucleoside diphosphates linked to other moieties, such as ADP-ribose. This cofactor is vital in redox reactions and is essential for the activity of sirtuins and poly(ADP-ribose) polymerases, which are involved in DNA repair and genomic stability. It has been shown that NUDT5 activity can also influence NAD+ homeostasis, thereby affecting cancer cell metabolism and survival. In this regard, the discovery of NUDT5 inhibitors has emerged as a potential therapeutic approach in cancer treatment. In this study, we conducted a high-throughput virtual screening of marine bacterial compounds against the NUDT5 enzyme and four molecules were selected based on their docking scores. These compounds established strong interactions within the NUDT5 active site, with molecular analysis highlighting the key role of Trp28A and Trp46B residues. Molecular dynamics simulations over 200 ns indicated a stable behavior, in association with root mean square deviation values always below 3 Å, suggesting conformational stability. Free energy landscape analysis further supported their potential as NUDT5 inhibitors, offering avenues for novel therapeutic strategies against NUDT5-associated breast cancer.

Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.

NUDT5 promotes the growth, metastasis, and Warburg effect of IDH wild-type glioblastoma multiforme cells by upregulating TRIM47

@#Objective: To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme (GBM). Methods: GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47 (TRIM47) in GBM patients. RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells. LN-229 cell proliferation, migration as well as invasion were estimated by CCK- 8, colony formation, wound healing, and Transwell assays following interference with NUDT5. ECAR assay, L-lactic acid kit, glucose detection kit, and ATP detection kit were applied for the detection of glycolysis-related indexes. Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47. Results: GEPIA database showed that NUDT5 expression was significantly increased in GBM patients. Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability, proliferation, invasion, migration, and glycolysis of GBM cells. Moreover, TRIM47 was highly expressed in GBM cells and interacted with NUDT5. Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation, metastasis, and glycolysis of GBM cells. Conclusions: NUDT5 promotes the growth, metastasis, and Warburg effect of GBM cells by upregulating TRIM47. Both NUDT5 and TRIM47 can be used as targets for GMB treatment.

Identification of promising inhibitors against breast cancer disease by targeting NUDIX hydrolase 5 (NUDT5) biomolecule.

It is well documented that NUDT5 enzyme inhibition in breast cancer cell lines arrest cancer cells growth, invasiveness and migration. The NUDT5 enzyme enhances breast cancer aggressiveness and act as key regulator of oncogenic pathways. Similarly, the NUDT5 enzyme plays a primer role in ATP-dependent cellular processes and proliferation in breast cancer. Thus, the NUDT5 enzyme plays a profound contribution in promoting breast cancers carcinogenesis and could be an ideal target for anti-cancer drug discovery. In this work, LAS_51382001, LAS_51177972 and LAS_51380924 with binding energy of -12.64 kcal/mol, -11.59 kcal/mol and -10.01 kcal/mol, respectively were filtered as lead molecules. The control molecule binding energy was -10.87 kcal/mol. The system dynamics were found uniform in molecular dynamics simulation studies and observed with no major structural changes. Among the leads, the LAS_51177972 showed the most stable binding energy values. The MM-GBSA binding energy of the compound was -37.07 kcal/mol and MM-PBSA binding energy of -43.56 kcal/mol. Similarly, the compound revealed very stable WaterSwap absolute binding energy values; Bennett's, TI and FEP energy of -36.2 kcal/mol, -36.13 kcal/mol and -36.58 kcal/mol, respectively. Similarly, the leads reported very favorable physicochemical properties, water solubility, pharmacokinetics, druglikeness and medicinal chemistry properties. In a nutshell, the compounds are potent in term of the current computational study however, need to be subjected to experimental studies.Communicated by Ramaswamy H. Sarma.

A novel m7G regulator-based methylation patterns in head and neck squamous cell carcinoma.

Abnormal RNA N7-methylguanosine (m7G) modification is known to contribute to effects on tumor occurrence and development. Nevertheless, the mechanisms of its function in immunoregulation, tumor microenvironment (TME) modulation, and tumor promotion remain largely unknown. A series of computer-aided bioinformatic analyses were conducted based on transcriptomic, single-cell sequence, and spatial transcriptomic data to determine the m7G modification patterns in head and neck squamous cell carcinoma (HNSCC). Consensus clustering approach was employed according to the expressions of 33 m7G regulators. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis algorithms were adopted to investigate the immune cell infiltration features. A prognostic model named m7Gscore was established. Seurat, SingleR, and Monocle2 were used to analyze the single-cell sequence profiling. STUtility was used to integrate multiple spatial transcriptomic datasets. Quantitative reverse transcription polymerase chain reaction, transwell, and wound-healing assay were performed to verify the oncogenes. Here, three different m7G modification patterns were highlighted in HNSCC patients, which were also related to various clinical manifestations and three representative immunophenotypes: immune-excluded, immune-desert, and inflamed, separately. Patients with lower m7Gscore were highlighted by higher immune cell infiltrations, better overall survival rates, lesser tumor mutation burden (TMB), lower sensitivities to target inhibitors therapies, and better immunotherapeutic response. Moreover, DCPS, EIF4E, EIF4E2, LSM1, NCBP2, NUDT1, and NUDT5 were identified to play critical roles in T-cell differentiation. Knockdown of LSM1/NUDT5 could restrain the malignancy of HNSCC cells. Collectively, quantitative assessment of m7G modification patterns in individual HNSCC patients could contribute to identifying more efficient immunotherapeutic approaches and improve the clinical outcome of HNSCC.

NUDT5-Determines the fate of head and neck squamous cell carcinoma cells under endoplasmic reticulum stress by catalyzing nuclear ATP production to promote DNA repair.

OBJECTIVES: NUDT5 is the only discovered enzyme that catalyses ATP production in cell nuclei. In this study, we investigate the character of NUDT5 in head and neck squamous cell carcinoma (HNSCC) cells under endoplasmic reticulum (ER) stress. METHODS: The formation of ER stress was confirmed in HNSCC cells using Real-time PCR and Western blot techniques. The expression of NUDT5 was modified by transfecting HNSCC cells with siRNA and plasmids, respectively. The effects of NUDT5 manipulation were assessed using various methods including cell counting kit-8 assay, western blotting, RNA sequencing, Immunofluorescence Microscopy analysis, cell cycle analysis and nucleic ATP measurement, and a xenograft mouse model. RESULTS: In this study, we found that the expression of NUDT5 proteins was upregulated under ER stress conditions in HNSCC cells. Knocking down NUDT5 under ER stress could hinder nuclear ATP generation and thus induce more DNA damage and apoptosis of HNSCC cells. Only the wild-type NUDT5 or ATP catalysis active mutant T45A-NUDT5, rather than the ATP catalysis null mutant T45D-NUDT5, could directly rescue nuclear ATP depletion caused by NUDT5 inhibition and protect HNSCC cells from DNA damage and cell apoptosis. Finally, in vivo studies showed that knocking down NUDT5 in ER-stressed conditions could significantly inhibit tumour growth. CONCLUSION: Our study demonstrated for the first time that NUDT5 guaranteed the integrity of DNA under ER stress-triggered DNA damage by catalysing nuclear ATP production. Our findings offer new insights into how the energy supply in cell nuclei fuels cancer cell survival in stressful microenvironment.

The ADP-ribose hydrolase NUDT5 is important for DNA repair.

DNA damage leads to rapid synthesis of poly(ADP-ribose) (pADPr), which is important for damage signaling and repair. pADPr chains are removed by poly(ADP-ribose) glycohydrolase (PARG), releasing free mono(ADP-ribose) (mADPr). Here, we show that the NUDIX hydrolase NUDT5, which can hydrolyze mADPr to ribose-5-phosphate and either AMP or ATP, is recruited to damage sites through interaction with PARG. NUDT5 does not regulate PARP or PARG activity. Instead, loss of NUDT5 reduces basal cellular ATP levels and exacerbates the decrease in cellular ATP that occurs during DNA repair. Further, loss of NUDT5 activity impairs RAD51 recruitment, attenuates the phosphorylation of key DNA-repair proteins, and reduces both H2A.Z exchange at damage sites and repair by homologous recombination. The ability of NUDT5 to hydrolyze mADPr, and/or regulate cellular ATP, may therefore be important for efficient DNA repair. Targeting NUDT5 to disrupt PAR/mADPr and energy metabolism may be an effective anti-cancer strategy.

Design, molecular docking, and molecular dynamics of thiourea-iron (III) metal complexes as NUDT5 inhibitors for breast cancer treatment.

In research, anticancer agents, such as thiourea derivative compounds, and metal complexes, such as those complexed with iron (III) metal, are often studied. The metal complexes are presumably more active than thiourea derivatives as free ligands; some negative effects may be reduced. The computational studies used in this study involved molecular docking with AutoDock and molecular dynamics (MD) simulations using Desmond to evaluate the stability of the interactions. The docking and MD analysis results showed that compounds 2 and 6 had stable interactions with NUDIX hydrolase type 5 (NUDT5)-one of the therapeutic targets for breast cancer-where they had the lowest root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values compared to the other compounds. Together, these compounds are anti-breast cancer drug candidates.

An efficient 2-aminothiazolesalicylaldehyde fluorescent chemosensor for Fe2+ ion detection and a potential inhibitor of NUDT5 signaling hormone for breast cancer cell and molecular keypad lock application.

A novel thiazole phenol conjugate, 2-aminothiazolesalicylaldehyde (receptor1) was designed and synthesized for the first time through a single step process via Schiff base condensation reaction. The formation of receptor1 was confirmed by FTIR, 13C NMR, and 1H NMR. The IR spectra confirmed the presence of the aldimine formation. It is further supported by the proton NMR, showing the disappearance of aldehyde peaks and the formation of a new imine peak. This is further corroborated by the 13C NMR. The receptor1 complexing with various metal ions were studied through fluorescence spectroscopy showed its selectivity toward Fe2+ ion following a reverse photoinduced electron transfer (PET) process compared to all other potentially competing ions. The receptor1 was applied as a sensor to sense Fe2+ ion in water samples. The detection limit for Fe2+ ion in drinking water was substantially lower (0.003 µM) than the EPA (environmental protection agency) recommendation (5.37 M). The capability of receptor1 in recovering Fe2+ ion in bore water, tap water, and drinking water was up to 99.5%. The receptor1 was also used as a chelating ligand (receptor1) in molecular docking and it was assessed as a potential inhibitor of NUDT5, a silence hormone signaling for breast cancer. The test compound (PDB: 5NWH) showed good affinity toward the target receptor1 with the binding energy of - 5.23 kcal mol-1. Furthermore, the receptor1 showed excellent reversibility property on adding EDTA solution. Due to the marvelous reversible property, a molecular-scale sequential information processing circuit is designed for the multi-task behavior such as 'Writing-Reading-Erasing-Reading' in the form of binary logic gate. The consecutive addition of Fe2+ ion and EDTA solution to receptor1 paves a way for the construction of INHIBIT logic gate. Additionally, the receptor1 showed the mimicking behavior of molecular keypad lock. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02373-z.

Silencing of Nudix type 5 represses proliferation and invasion and enhances chemosensitivity of gastric carcinoma cells by affecting the AKT/GSK-3ß/ß-catenin pathway.

Nudix type 5 (NUDT5) has been recently identified as a new cancer-associated protein that is involved in numerous cancers. To date, the relationship between NUDT5 and gastric carcinoma has not been addressed. In the current research, we focused on exploring the potential relevance of NUDT5 in gastric carcinoma. The initial analysis of NUDT5 expression in gastric carcinoma by TCGA data revealed a clear increase in NUDT5 expression in tumor versus normal tissue. The increased expression of NUDT5 was also validated in the clinical specimens of gastric carcinoma by immunoblotting detection. Moreover, high NUDT5 levels predicted a poorer overall survival in gastric carcinoma patients. A series of cellular functional assays demonstrated that gastric carcinoma cells with silenced NUDT5 exhibited decreased proliferative and invasive ability, increased cell cycle arrest at the G0/G1 phase, and enhanced chemosensitivity. In-depth research showed that the silencing of NUDT5 led to a reduction in the activation of AKT and ß-catenin. The reactivation of AKT blocked the repressive effect of NUDT5 silencing on ß-catenin activation. The forced expression of ß-catenin also reversed NUDT5-silencing-mediated anticancer effects. A Xenograft tumor assay confirmed the anticancer role of NUDT5 in gastric carcinoma in vivo. In short, these findings reveal elevated NUDT5 levels in gastric carcinoma and demonstrate that the inhibition of NUDT5 displays promising anticancer effects by affecting the AKT/ß-catenin pathway. Thus, our work unveils a vital role of NUDT5 in gastric carcinoma and indicates it as a viable candidate target for anticancer drug discovery.

LASSO-based screening for potential prognostic biomarkers associated with glioblastoma.

Background: Glioblastoma is the most common malignancy of the neuroepithelium, yet existing research on this tumor is limited. LASSO is an algorithm of selected feature coefficients by which genes associated with glioblastoma prognosis can be obtained. Methods: Glioblastoma-related data were selected from the Cancer Genome Atlas (TCGA) database, and information was obtained for 158 samples, including 153 cancer samples and five samples of paracancerous tissue. In addition, 2,642 normal samples were selected from the Genotype-Tissue Expression (GTEx) database. Whole-gene bulk survival analysis and differential expression analysis were performed on glioblastoma genes, and their intersections were taken. Finally, we determined which genes are associated with glioma prognosis. The STRING database was used to analyze the interaction network between genes, and the MCODE plugin under Cytoscape was used to identify the highest-scoring clusters. LASSO prognostic analysis was performed to identify the key genes. Gene expression validation allowed us to obtain genes with significant expression differences in glioblastoma cancer samples and paracancer samples, and glioblastoma independent prognostic factors could be derived by univariate and multivariate Cox analyses. GO functional enrichment analysis was performed, and the expression of the screened genes was detected using qRT-PCR. Results: Whole-gene bulk survival analysis of glioblastoma genes yielded 607 genes associated with glioblastoma prognosis, differential expression analysis yielded 8,801 genes, and the intersection of prognostic genes with differentially expressed genes (DEG) yielded 323 intersecting genes. PPI analysis of the intersecting genes revealed that the genes were significantly enriched in functions such as the formation of a pool of free 40S subunits and placenta development, and the highest-scoring clusters were obtained using the MCODE plug-in. Eight genes associated with glioblastoma prognosis were identified based on LASSO analysis: RPS10, RPS11, RPS19, RSL24D1, RPL39L, EIF3E, NUDT5, and RPF1. All eight genes were found to be highly expressed in the tumor by gene expression verification, and univariate and multivariate Cox analyses were performed on these eight genes to identify RPL39L and NUDT5 as two independent prognostic factors associated with glioblastoma. Both RPL39L and NUDT5 were highly expressed in glioblastoma cells. Conclusion: Two independent prognostic factors in glioblastoma, RPL39L and NUDT5, were identified.

Design of Novel Coumarin Derivatives as NUDT5 Antagonists That Act by Restricting ATP Synthesis in Breast Cancer Cells.

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2R)-2-((S)-sec-butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1H-pyrrol-3-olate was designed. Molecular docking studies provided a docking score of -6.574 kcal/mol and an MM-GBSA value of -29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be -75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC50 value of 55.57 (+/-) 0.7 µg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity.

Role of the NUDT Enzymes in Breast Cancer.

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

The high expression of MTH1 and NUDT5 promotes tumor metastasis and indicates a poor prognosis in patients with non-small-cell lung cancer.

MutT Homolog 1 (MTH1) is a mammalian 8-oxodGTPase for sanitizing oxidative damage to the nucleotide pool. Nudix type 5 (NUDT5) also sanitizes 8-oxodGDP in the nucleotide pool. The role of MTH1 and NUDT5 in non-small-cell lung cancer (NSCLC) progression and metastasis remains unclear. In the present study, we reported that MTH1 and NUDT5 were upregulated in NSCLC cell lines and tissues, and higher levels of MTH1 or NUDT5 were associated with tumor metastasis and a poor prognosis in patients with NSCLC. Their suppression also restrained tumor growth and lung metastasis in vivo and significantly inhibited NSCLC cell migration, invasion, cell proliferation and cell cycle progression while promoting apoptosis in vitro. The opposite effects were observed in vitro following MTH1 or NUDT5 rescue. In addition, the upregulation of MTH1 or NUDT5 enhanced the MAPK pathway and PI3K/AKT activity. Furthermore, MTH1 and NUDT5 induce epithelial-mesenchymal transition both in vitro and in vivo. These results highlight the essential role of MTH1 and NUDT5 in NSCLC tumor tumorigenesis and metastasis as well as their functions as valuable markers of the NSCLC prognosis and potential therapeutic targets.

Identification of NUDT5 Inhibitors From Approved Drugs.

Recent studies have revealed the important role of NUDT5 in estrogen signaling and breast cancer, but research on the corresponding targeted therapy has just started. Drug repositioning strategy can effectively reduce the time and economic resources spent on drug discovery. To find novel inhibitors of NUDT5, we investigated the previously identified connectivity map-based drug association models and found eighteen FDA approved drugs as candidates. The molecular docking and molecular dynamic simulation were performed and revealed that fourteen organic drugs have the potential to bind the NUDT5 target. Eight representative drugs were selected to perform the cell line viability inhibition analysis, and the results showed that seven of them were able to suppress MCF7 breast cancer cells. Two drugs, nomifensine and isoconazole, showed lower IC50 than the known antiestrogens raloxifene and tamoxifen, and they deserve further pharmacodynamic investigations to test their feasibility for use as NUDT5 inhibitors.

miR-339-5p inhibits NUDT5 and enhances radiosensitivity of lung cancer A549 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the influence of miR-339-5p on the radio-sensitivity of lung cancer A549 cells by regulating the expression of Nudix hydrolase 5 (NUDT5). Methods: X-ray-resistant lung cancer A549 cells (RA549) were induced by treatment with low concentration gradient increment combined with large dose intermittent shock in vitro. The expression level of miR-339-5p in hu‐ man normal lung epithelial cells (BEAS-2B) and lung cancer cell lines (A549, L78, H1299, H460 and RA549 cells) was detected by qP‐ CR. According to the treatment, RA549 cells were divided into NC group, 5Gy group (treatment with 5Gy X-ray), 5Gy+miR-339-5p mimic group, 5Gy+si-NUDT5 group and 5Gy+si-NUDT5+miR-339-5p inhibitor group. CCK-8 assay, Annexin V-FITC/PI double stain‐ ing flow cytometry and WB were used to detect the proliferation, apoptosis and the protein expressions of NUDT5, γ-H2AX and H2AX in each group. The targeting relationship between mir-339-5p and NUDT5 was detected by Dual-luciferase reporter gene system. Results: The expression of miR-339-5p in lung cancer cell lines was significantly lower than that in BEAS-2B cells, with the lowest ex‐pression level in RA549 cells (all P<0.05). NUDT5 was the target gene of miR-339-5p. Compared with the NC group, the prolifera‐ tion activity and NUDT5 expression of RA549 cells in the 5 Gy group were significantly reduced (all P<0.01), and the apoptosis rate was significantly increased (P<0.01). Compared with the 5 Gy group, the proliferation activity of RA549 cells in the 5 Gy+miR-339-5p mimic group was significantly reduced (P<0.05), the apoptosis rate ([12.97±1.48]% vs [5.21±0.62]%, P<0.01) and the expression level of γ-H2AX (P<0.05) were significantly increased; the expression of NUDT5 (t=7.58, P<0.01) and cell proliferation activity (t=6.58, P<0.01) of RA549 cells in the 5 Gy+si-NUDT5 group were significantly reduced, while the apoptosis rate ([11.21±1.06]% vs [5.54±0.44%, P<0.01) and the expression of γ-H2AX (P<0.01) were significantly increased; and the above indicators in 5 Gy+si-NUDT5+miR-339-5p inhibitor group showed insignificant difference from the 5 Gy group. Conclusion: Overexpression of miR-339-5p enhances the radio-sensitivity of X-ray-resistant lung cancer A549 cells by targetedly down-regulating NUDT5 expression.

Molecular docking based virtual screening of the breast cancer target NUDT5.

Breast cancer affects one in eight women in Bangladesh and is the most common cancer among women in South Asia next to skin cancer. NUDT5 are nucleotide-metabolizing enzymes (NUDIX hydrolases) linked with the ADP ribose and 8-oxo-guanine metabolism. It is known to be associated with the hormone dependent gene regulation and proliferation in breast cancer cells. It blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in this context. We describe the structure based binding features of a lead compound (7-[[5-(3, 4-dichlorophenyl)-1,3,4-oxadiazol-2-yl]methyl]-1,3-dimethyl-8piperazin-1yl-purine-2,6-dione-C20H20Cl2N8O3) with NUDT5 for further in vitro and in vivo validation. It is a promising inhibitor for blocking NUDT5 activity. Thus, structure based virtual screening is used to identify a potential therapeutic inhibitor for NUDT5.