Extended Data Fig. 5. Pharmacologic assessment of nintedanib targets.

a, Combinatorial drug screen on mesenchymal hPDAC cell line MiaPaca2 and mPDAC cell line 9091, as shown in Figure 2, panel (b). The MEK inhibitor trametinib was used in fixed concentration and combined with 418 additional drugs under preclinical and clinical investigation. Highlighted in orange are the drugs in the high-throughput drug screen showing overlapping targets with nintedanib.

b, Venn diagrams showing the target overlap between the drugs identified in (a) and nintedanib (see supplementary table 4) as reported from the ProteomicsDB database (https://www.proteomicsdb.org).

c, Venn diagrams showing the target overlap between nintedanib and additional drugs with an overlapping target profile chosen for further target assessment. The overlapping targets are listed below each figure. The target information was downloaded from the ProteomicsDB database (https://www.proteomicsdb.org).

d, Representative clonogenic assays of mesenchymal mPDAC cell cultures treated with trametinib in combination with the drugs shown in (c) as compared to nintedanib. The cell lines were treated with the indicated concentrations of trametinib and the indicated experimental drug.

e, Bliss synergy scores of clonogenic assays shown in (d) integrated with cell morphology for the treated mPDAC cell cultures (classical subtype depicted in yellow and mesenchymal in blue).