Nintedanib analogs target KIT D816V hematopoietic cells. (A) The impact of 43 nintedanib analogs on KIT D816V and control iPSC–derived hematopoietic cells was determined using CellTiter Glo assays (1 µM of compound) and is shown as the percentage of untreated cells. KIT D816V selective compounds are highlighted and color coded. Dotted lines indicate response to nintedanib treatment. (B) Representative drug response curves for KIT D816V and control iPSC–derived hematopoietic cells treated with BIBG1724TF, BIBE3315BS, BIBF1496XX, or BIBE3316BS. IC50 values were 96 to 203 nM and 849 to 917 nM for KIT D816V and control cells, respectively. (C) Averaged drug response ± standard deviation of KIT D816V iPSC–derived hematopoietic cells treated with 1 µM BIBG1724TF, BIBF1496XX, BIBE3315BS, or BIBE3316BS show a significant decrease in cell viability in comparison with treated control cells (n = 6-9). *P < .0001, Welch’s t test. (D) Structures and interactions based on protein-ligand interaction fingerprint, as described in supplemental Figure 24B. Lys593, Glu605, Lys623, Glu671, and Cys673 establish H-bond interactions with the ligands. Val603/Gly676 and Phe811 establish H-arene interactions and aromatic interactions, respectively, with the aromatic moieties of the ligands. These interactions are represented as circles because they are spread over all of the atoms of the aromatic rings. The colors uniquely identify each residue but do not refer to the kind of interaction established.