A series of novel acridane-based tubulin polymerization inhibitors were designed, synthesized, and bioevaluated as anticancer agents. The most potent compound exhibited high tubulin polymerization inhibitory activity (IC = 1.5 μM) and remarkable antiproliferative potency against four cancer cell lines with an average IC of 30 nM, better than colchicine and the hit compound (IC of 65 and 126 nM, respectively). In addition, (10 mg/kg) exerted excellent antitumor efficacy in a melanoma tumor model with a tumor growth inhibition (TGI) of 65.1% without apparent toxicity. Importantly, the combination of with a small-molecule PD-L1 inhibitor NP-19 decreased tumor burden significantly (TGI% = 77.6%). Moreover, the combination of with NP-19 enhanced the antitumor immune response, mediated by a decrease of PD-L1 expression levels and increased infiltration of antitumor CD8 effector T cells in tumor tissues. Collectively, represents a novel tubulin polymerization inhibitor with immunopotentiating effects.
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