Fig. 2: Meriolin 16 and 36 inhibit CDK1, 2, and 9 and inhibit a variety of other kinases in a kinome screen with a prevalence to the CMGC family.

A luminescence-based kinase activity assay was used to determine the inhibitory activity of meriolin 16 and 36 on selected CDKs and their corresponding cyclins with the usage of CDK Kits from BPS Bioscience (A) CDK1/cyclin B1; (B) CDK2/cyclin A2; (C) CDK9/cyclin T. In this kinase assays, the relative luminescence correlates with the inhibitory capacity of the treatment and concentration, respectively. DMSO (0.1% v/v) was used as solvent control and R547 as positive control (Selleckchem.com: inhibitor of CDK1/2 and 4). Error bars = mean ± SD values of three independent biological experiments are shown. Statistical analysis: one-way ANOVA, Bonferroni’s multiple comparison test; (****p ≤ 0.0001). D Kinome screening with meriolin 16 and 36. Kinase inhibition by meriolin 16 (0.03 µM and 0.3 µM) and meriolin 36 (0.3 µM and 3 µM) is depicted as kinome tree. The diameter of dots reflects % inhibition of 335 kinases (atypical kinases DNAPK, EEF2K mTOR and PKMzeta were excluded), the scale is 0 to ≥100% inhibition. E Heatmap of the CDK/cyclin family with the residual kinase activity upon inhibition with meriolin 16 (0.03 µM and 0.3 µM) and meriolin 36 (0.3 µM and 3 µM). This heat map shows kinase inhibition by meriolins from dark blue (maximum inhibition of the kinase, 0%) to white (maximum kinase activity, 100%). F Shown in this table are the selectivity scores which were calculated for both concentrations of meriolin 16 (0.03 µM and 0.30 µM) and meriolin 36 (0.30 µM and 3.00 µM).