Fig. 4. Selective dual inhibitors of CDK8/19.

Target engagement at CDK8/19 (upper panels) with compounds CCT251545 (a), BMS-265246 (b), and K03861 (c). CDK2 is included in each graph for comparative reference. Each graph shows a single representative technical replicate (n = 1) from 3 independent experiments (Supplementary Data 2). Lower: Compound structures and dendrogram-based illustration of engagement selectivity for CCT251545, BMS-265246, and K03861 against the complete CDK family D. Representative live cell engagement potency for CDK8/19-selective compounds. Reported IC₅₀ data are the mean of 3 independent experiments ± S.E.M. (Supplementary Data 2). Blank cells represent IC₅₀ values that failed to meet our criteria of potency (<1 µM) or occupancy (≥50% at 10 µM). Source data are provided as a Source Data file.