FIGURE 1 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

NCATS screening identifies TAK-243 as one of the most potent drugs against ACC cell lines. A, CU-ACC1, CU-ACC2, and NCI-H295R cell lines were screened with the NCATS MIPE v5.0 (MIPE 5.0) library of approved and investigational drugs (n = 2,480). Drugs with Z-AUC values less than −1.5 and good-quality dose–response curves were selected. The number of drugs effective in the three cell lines is shown in the Venn diagram (left). The 21 drugs commonly effective in the three cell lines and their mechanism of action were tabulated. B, Drugs were arranged in Z-AUC order for the three cell lines tested, with red dots indicating TAK-243. The positions of mitotane, doxorubicin, and etoposide were also shown. C, Heat map of IC₅₀ values of selected drugs with highest and lowest activity against the three ACC cell lines and SW-13 (small cell carcinoma cell line of adrenocortical origin). Drug targets were listed in parentheses.