Az 20

For treatment with the ATR inhibitor AZ-20 (AstraZeneca), 5000 cells were seeded per well in a 96-well tissue culture plate and increasing concentrations of AZ-20 added to the media. Cell viability was assessed after 48 h using a luminescent system (CellTiter-Glo, Promega), according to the manufacturer's protocol. For proliferation assays, 4000 cells (WT, PDS5A KO, or PDS5B KO) or 8000 cells (PDS5A KO+shB, incubated with doxycycline for 72 h before seeding) were seeded per well in 96-well tissue culture plate at day 0. Proliferation was monitored for the following 4 days using a colorimetric assay (CellTiter 96 AQueous One Solution Cell Proliferation Assay, Promega).

AZ31, AZ20, AZD2281, AZD2811, AZD7648, TLR1 (WO2014183850), M9831/VX-984, FEN-IN-1, PolQi1 (WO2021/028643, Example 158), PolQi2 (WO2020/243459, Example 99) were provided by AstraZeneca (Gothenburg, SE). Three of the DNA-PK inhibitors, AZD7648 (HY-111783, MedChemExpress), M9831/VX-984 (HY-19939S, MedChemExpress) and M3814 (S8586, Selleckchem) are commercially available. Nu7026 and KU0060648 were purchased from Sigma-Aldrich (N1537, SML1257). Novobiocin, ART558 and AZD7648 were obtained from MedChemExpress (HY-B0425A, HY-141520 and HY-111783). SCR7 was purchased from Selleckchem (S7742). All compounds were dissolved in DMSO (Thermo Fisher Scientific) at a concentration of 10 mM.