Fig. 2: Optimization of dCK inhibitors with improved affinity, enzymatic inhibition and cellular activity. | Nature Communications

Fig. 2: Optimization of dCK inhibitors with improved affinity, enzymatic inhibition and cellular activity.

From: From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia

Fig. 2: Optimization of dCK inhibitors with improved affinity, enzymatic inhibition and cellular activity.The alternative text for this image may have been generated using AI.

a Effect on dCK thermal stabilization (determined by TSA) and dCK cell proliferation assay (CCRF-CEM cell line) produced by the 74 synthetized compounds. Data are presented as the mean. b dCK thermal stabilization by selected compounds measured by TSA. Data are presented as the mean ± SD (n = 3). c Representative curves of one of two independent experiments showing the effect of selected compounds on substrate phosphorylation by dCK in the presence of ATP. Data are presented as the mean of three technical replicates ± SD. d Representative experiment showing the effect of selected compounds on cell proliferation of the CCRF-CEM cell line in the presence of dT (200 µM) and dC (1 µM) Data are presented as the mean ± SD (n = 3). e Chemical structure of OR0642. f Structure of dCK (gray ribbon) in complex with OR0642 (magenta) and UDP (yellow) (PDB 7ZI3) showing the hydrogen bond network to dCK (black dashed lines). VdW interactions between OR0642 CF3 group and dCK ILE-200 and PRO-201 are shown as green dashed lines in the zoom insert. g The meshes around the compound shows the |2Fo|−|Fc| electron density map contoured at 2.0σ around the ligand (blue) and the |Fo|−|Fc| electron density map (orange) contoured at 1.0σ generated with the model compound omitted before refinement (omit map).

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