Azd7648

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.

Human cell lines were purchased from ATCC and cultured in Dulbecco’s modified Eagle’s medium (DMEM; ThermoFisher#41966029) (MIA PaCa-2, PANC-1 and HPAF-II) or RPMI-1640 (ThermoFisher#21875034) (AsPC-1) plus 10% foetal bovine serum (FBS; ThermoFisher#10270106). Murine cell lines K8484 and DT8082 were previously established from KPC mice of 129/SvJae/C57Bl/6 background in the laboratory of David Tuveson at the CRUK Cambridge Institute²² and were grown in DMEM with 5% FBS. Lines were subjected to regular STR fingerprinting and mycoplasma tests, performed by the CRUK-CI Cell Services core facility. AZD6738, AZD0156 and AZD7648 were provided by AstraZeneca. These, plus gemcitabine hydrochloride (Tocris#3259), were dissolved in dimethyl sulfoxide (DMSO) for in vitro experiments, kept at −20 °C and used within 3 months.