DNPH1i

DNPH1i is an inhibitor of 2’-deoxynucleotide 5’-phosphate N-hydrolase 1 (DNPH1).¹ It inhibits DNPH1 activity toward the DNPH1 substrate 5-hydroxymethyl-2’-deoxyuridine (hmdU) when used at a concentration of 100 µM. DNPH1i (0.3 µM) reduces the viability of BRCA1-deficient SUM149 cells containing single-guide RNA against p53-binding protein 1 (sg53BP1) when used in combination with hmdU but not when used alone. It also reduces the viability of hematological cancer cells, including CEM, HL-60, K562, and RPMI-8226 cells (IC₅₀s = 1.3, 0.93, 5.9, and 4.6 µM, respectively), solid tumor cells, including MCF-7, HeLa, and HOS cells (IC₅₀s = 3.7, 1.9, and 13.6 µM, respectively), and G-361 malignant melanoma cells (IC₅₀ = 15 µM) but also reduces viability of BJ fibroblasts (IC₅₀ = 1.7 µM).²

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1. Fugger, K., Bajrami, I., Silva Dos Santos, M., et al. Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors. Science 372(6538), 156-165 (2021).

2. Voller, J., Zatloukal, M., Lenobel, R., et al. Anticancer activity of natural cytokinins: A structure-activity relationship study. Phytochemistry 71(11-12), 1350-1359 (2010).