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DCZ0415 is an inhibitor of thyroid hormone receptor interactor 13 (TRIP13).1 It binds to TRIP13 (Kd = 2.42 µM) and reduces non-homologous end joining (NHEJ) repair of DNA in a reporter assay. DCZ0415 (10 and 20 µM) impairs DNA repair in ARP-1 and NCI H929 multiple myeloma cells. It reduces the growth of a variety of multiple myeloma cells, including RPMI-8226, ARP-1, and ARK cells (IC50s = 7.4, 5.12, and 3.25 µM, respectively) and induces apoptosis in ARP-1 cells. DCZ0415 (50 mg/kg per day) induces intratumoral apoptosis and impairs intratumoral DNA repair, reduces tumor volume, and increases survival in an NCI H929 mouse xenograft model.
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1. A small-