Au (I)-based drugs - sodium aurothiomalate and aurothioglucose – are selective and potent zinc-finger inhibitors of PARP-1
Data files
Apr 29, 2026 version files 5.24 MB
-
AU_compounds.opju
2.49 MB
-
AU_paper_brdU_assay.opju
952.99 KB
-
AU_paper_resistant_cell_line.opju
1.35 MB
-
PARP1_Km.opju
434.54 KB
-
README.md
1.62 KB
Abstract
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.
Dataset DOI: 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, fitting and statistics of PARP-1 inhibition obtained by PARP activity assay
File: AU_paper_brdU_assay.opju
Description: raw data, fitting and statistics of UWB 1.289 proliferation obtained by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay,
File: AU_paper_resistant_cell_line.opju
Description: raw data, fitting and statistics of viability of HCC1937 cell line measured by CellTiter Glo Luminescence cell viability assay
File: PARP1_Km.opju
Description: raw data, fitting and statistics of IC50 for PARP-1 inhibitors obtained by PARP activity assay
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 the number of viable cells in culture based on quantitation of the ATP present, an indicator of metabolically active cells. The plates were read by PHERAstar FS Plate Reader (BMG Labtech). The percent viability was calculated as: % = 100 x (Luminescence untreated – Luminescence treated) / ( Luminescence untreated – Luminescence blank).
Cell Cultures. UWB 1.289 and HCC1937 cell lines were obtained from ATCC and cultivated according to the handling instructions.
Data analysis and fitting was performed in Excel and OriginTM. Values given as mean ± s.e.m.