Au (I)-based drugs - sodium aurothiomalate and aurothioglucose – are selective and potent zinc-finger inhibitors of PARP-1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a multidomain enzyme essential for the DNA damage response; its inhibition can lead to cancer cell death. Recruitment of PARP-1 to sites of genomic damage is mediated by its zinc finger domains. In this study, we investigated the inhibition of PARP-1’s DNA-dependent activation by three Au(I)-based drugs, presumable zinc-ejectors. We found that aurothioglucose and sodium aurothiomalate selectively inhibited PARP-1’s DNA-dependent activity, with IC50 values in the nanomolar range, while preserving its DNA-independent activity. Furthermore, in a BRCA-mutated cell line, both compounds effectively suppressed DNA replication, with half-maximal effective concentrations (EC50) also in the nanomolar range. These findings highlight the potential of selective, zinc finger–targeting PARP-1 inhibitors as promising therapeutic agents. , PARP assay. PARP-1 and PARP-2 activity and inhibition was measured using the PARP1-Enzyme-Activity-Assay as a direct fluorescence-based concentration measurement of reaction product formation.  The assay reagents are sold as a commercial kit (17-10149, Merck Millipore).  PARP activity and inhibition was measured for human full length recombinant active PARP-1 (CS207770, Merck) and  PARP-2 (ab198766, Abcam). 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay. BrdU was incorporated into DNA of replicating UWB1.289 cells by substituting thymidine, and BrdU containing DNA was subsequently detected with BrdU-specific antibodies. The percentage of DNA replication was calculated as: % = 100% x (Absorbance untreated) / (Absorbance untreated); the untreated cells were assumed to demonstrate 100% DNA replication activity.  CellTiter Glo Luminescence cell viability assay. The CellTiter-Glo® Luminescent Cell Viability Assay (Promega) is a homogeneous method of determining t..., # Au (I)-based drugs - sodium aurothiomalate and aurothioglucose – are selective and potent zinc-finger inhibitors of PARP-1 Dataset DOI: [10.5061/dryad.f1vhhmh7x](10.5061/dryad.f1vhhmh7x) ## Description of the data and file structure This dataset contains the data and analysis obtained by **PARP activity assay,** kit 17-10149, Merck Millipore, **see Materials**, showing calculation of: * PARP-1 Km (**one file**: “*PARP1_Km.opju*”) * IC50 for PARP-1 inhibitors (**one file**: “*AU_compounds.opju*”) This dataset also contains the data and analysis of UWB 1.289 cells proliferation obtained by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay, **see Materials: one file** “*AU paper_brd_assay.opju*” This dataset also contains the data and analysis viability of HCC1937 cells measured by CellTiter Glo Luminescence cell viability assay, **see Materials**: **one file** “*AU paper_resistant_cell_line.opju*” ### Files and variables #### File: AU_compounds.opju **Description:** raw data, ..., ,