Antitumor and antiangiogenic activity of the novel chimeric inhibitor animacroxam in testicular germ cell cancer

摘要: Chimeric inhibitors, which merge two drug pharmacophores in a single molecule have become prominent approach for the design of novel anticancer compounds. Here, we examined animacroxam, combines histone deacetylase (HDAC) inhibitory and cytoskeleton-interfering pharmacophores, testicular germ cell tumors (TGCT). The effectiveness animacroxam was compared to that commonly applied chemotherapeutic cisplatin as well clinically approved HDAC inhibitor vorinostat. antineoplastic antiangiogenic effects on TGCT vivo were assessed through exploratory animal studies modified chorioallantoic membrane assay, revealing has significant antitumor activity TGCT. A positron emission tomography/MR-imaging determine tumor volume glucose [2-fluoro-2-deoxy-d-glucose (18F-FDG)] uptake tumors, reduced animacroxam-treated TGCTs showing dose-dependent suppression glycolytic enzymes, led breakdown energy production. Furthermore, observed related its ability inhibit endothelial cell-cell communication, expression gap junction-forming connexin 43 strongly suppressed, gap-junctional intercellular mass transport reduced. Our data suggest chimeric may promising candidate treatment solid cancers serve an interesting alternative platinum-based therapies.