ArticleJournal of biomolecular screening2015
A High-Throughput Enzyme-Coupled Assay for SAMHD1 dNTPase.
Article in Journal of biomolecular screening, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- ssDNA and ssRNA Promote Phase Condensation of SAMHD1.Biochemistry · 2025Article
- Inhibitors of SAMHD1 Obtained from Chemical Tethering to the Guanine Antiviral Acyclovir.Biochemistry · 2025Article
- Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel.iScience · 2024Article
- Deoxyguanosine-Linked Bifunctional Inhibitor of SAMHD1 dNTPase Activity and Nucleic Acid Binding.ACS chemical biology · 2023Article
- Discovery and characterization of a novel cGAS covalent inhibitor for the treatment of inflammatory bowel disease.Acta pharmacologica Sinica · 2023Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- Antibacterial Target DXP Synthase Catalyzes the Cleavage of d-Xylulose 5-Phosphate: a Study of Ketose Phosphate Binding and Ketol Transfer Reaction.Biochemistry · 2022Article
- Differences between intrinsic and acquired nucleoside analogue resistance in acute myeloid leukaemia cells.Journal of experimental & clinical cancer research : CR · 2021Article
- Dual roles of SAMHD1 in tumor development and chemoresistance to anticancer drugs.Oncology letters · 2021Review
- Probing the Catalytic Mechanism and Inhibition of SAMHD1 Using the Differential Properties of RBiochemistry · 2021Article
- Spectral Unmixing-Based Reaction Monitoring of Transformations between Nucleosides and Nucleobases.Chembiochem : a European journal of chemical biology · 2020Article
- The C-terminal domain of feline and bovine SAMHD1 proteins has a crucial role in lentiviral restriction.The Journal of biological chemistry · 2020Article
- Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.EMBO molecular medicine · 2020Article
- Chromatin-bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death.The EMBO journal · 2019Article
- Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML.Nature communications · 2019Article
- A UV/Vis Spectroscopy-Based Assay for Monitoring of Transformations Between Nucleosides and Nucleobases.Methods and protocols · 2019Article
- SAMHD1 Suppression of Antiviral Immune Responses.Trends in microbiology · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a recently discovered enzyme that plays a central role in nucleotide metabolism and innate immunity. SAMHD1 has deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase activity that depletes the dNTP substrates required for DNA synthesis in cells. The involvement of SAMHD1 in biological processes as varied as viral restriction, endogenous retroelement control, cancer, and modulation of anticancer/antiviral nucleoside drug efficacy makes it a valuable target for the development of small-molecule inhibitors. We report a high-throughput colorimetric assay for SAMHD1 dNTP hydrolase activity that takes advantage of Escherichia coli inorganic pyrophosphatase to convert PPPi to 3 Pi. The assay was validated by screening a library of 2653 clinically used compounds. Fifteen primary hits were obtained (0.57% hit rate); 80% of these were confirmed in a direct secondary assay for dNTP hydrolysis. The zinc salt of the antibiotic cephalosporin C was a potent inhibitor of SAMHD1 with an IC50 of 1.1 ± 0.1 µM, and this inhibition was largely attributable to the presence of zinc. The assay also screened a targeted library of nucleosides and their analogs, revealing that the antiviral drug acycloguanosine (acyclovir) is an inhibitor possessing excellent properties for future fragment-based drug development efforts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.