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. Author manuscript; available in PMC: 2020 Mar 1.
Published in final edited form as: Mol Cancer Ther. 2019 Jun 18;18(9):1506–1519. doi: 10.1158/1535-7163.MCT-18-0571

Figure 6: AD80 is isoform biased for p38γ and p38δ, over p38α and p38β, with binding dependent on the gatekeeper residue.

Figure 6:

A. Chemical structure of AD80 and related compounds. B. Cell viability assay comparing activity of each compound on the HUH7 cell line. Technical replicates n=6. C. Hierarchical clustering of previously generated in vitro inhibitory profiles (ref. (28)) of the most different kinases between the related compounds. D-E. Melting temperature binding assay using a 1:1 ratio of drug to protein (ie. 5 μM drug to 5 μM protein). Each point is the difference in mean melting temperature (technical replicates: n=6) as determined by differential scanning fluorimetry. In E the following mutations at the gatekeeper residue were tested: p38α/MAPK14 T106M, p38β/MAPK11 T106M, p38γ/MAPK12 M109T, p38δ/MAPK13 M107T.