FIGURE 8 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

TAK-243 inhibits tumor growth in ACC xenograft models and synergizes with the BCL2 inhibitor Venetoclax. A, H295R xenografts were treated with TAK-243 (10 and 20 mg/kg) intraperitoneally twice weekly and mean tumor volume was evaluated. Error bars indicate SEM (n = 5); tumor volume for each mouse on day 29 was shown individually on the right. B, Xenograft tissues collected on day 29 (H&E staining, immunostaining for anti-multi-ubiquitin and anti-cleaved caspase-3 antibodies). Top panel: control, bottom panel: TAK-243 (20 mg/kg) group. Scale bar: 200 µm. C, Left: CU-ACC1 xenografts were treated with TAK-243 (10 mg/kg) intraperitoneally twice weekly, venetoclax (100 mg/kg) orally five times weekly, and a combination of TAK-243 and venetoclax, and mean tumor volume was evaluated. Error bars indicate SEM (n = 5); tumor volume of each mouse on day 29 was shown separately. Right: Tumor weight of each treatment group on day 29. Horizontal lines indicate mean values and error bars indicate SEM.