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NIC3 is an inhibitor of nucleus accumbens–associated protein-1 (NAC1) homodimerization. Specifically, NIC3 has the ability to selectively bind with the conserved Leu90 of NAC1 and to inhibit NAC1 dimerization, resulting in proteasomal degradation of the NAC1 protein. NIC3 shows potent effects on sensitizing drug-resistant tumor cells to chemotherapy and reinforcing the antimetastatic efficacy of the antiangiogenic agent bevacizumab.