DCZ0415

DCZ0415, a potent TRIP13 inhibitor, impairs nonhomologous end joining repair and inhibits NF-κB activity. DCZ0415 induces anti-myeloma activity in vitro, in vivo, and in primary cells derived from drug-resistant myeloma patients[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

NF-κB

DCZ0415 (10, 20 μM; 72 hours) shows a significant decrease in colony formation, indicating it inhibits cell proliferation[1]. DCZ0415 (1.25-40 μM; 72 hours) induces a significant dose-dependent decrease of viability inMM cells[1]. DCZ0415 (10, 20 μM; 24-72 hours) shows a dose-dependent relationship between DCZ0415 treatment and apoptotic cell death[1]. DCZ0415 (10, 20 μM; 24 hours) induces a significant accumulation in G0/G1 MM cells[1]. DCZ0415 (10 μM; 48 hours) decreases the protein levels of phosphorylated (p)-iκBα and phosphorylated (p)-NF-κB in MM cells[1]. DCZ0415 has IC50s of 1.0–10 μM in CalcuSyn in MM cell lines[1]. DCZ0415 exerts cytotoxic effects by inhibiting DNA 288 synthesis in MM cells[1]. Cell Proliferation Assay[1] Cell Line: Multiple myeloma (MM) cells Concentration: 10, 20 μM Incubation Time: 72 hours Result: Showed a significant decrease in colony formation, indicating it inhibits cell proliferation. Cell Viability Assay[1] Cell Line: MM cells Concentration: 1.25, 2.5, 5, 10, 20, 40 μM Incubation Time: 72 hours Result: Induced a significant dose-dependent decrease of viability. Apoptosis Analysis[1] Cell Line: MM cells Concentration: 10, 20 μM Incubation Time: 24, 48, 72 hours Result: Showed a dose-dependent relationship between DCZ0415 treatment and apoptotic cell death. Cell Cycle Analysis[1] Cell Line: MM cells Concentration: 10 and 20 μM Incubation Time: 24 hours Result: Induced a significant accumulation in G0/G1 MM cells. Western Blot Analysis[1] Cell Line: MM cells Concentration: 10 μM Incubation Time: 48 hours Result: Decreased the protein levels of phosphorylated (p)-iκBα and phosphorylated (p)-NF-κB in MM cells.

DCZ0415 (ip; 50 mg/kg/day for 14 days) significantly reduces the growth of MM cells-induced tumors in immune-deficient mice[1]. Animal Model: Nude mice (6-weeks-old) with H929 775 cells[1] Dosage: 50 mg/kg Administration: Intraperitoneal injection; every day for 14 days Result: Significantly reduced the growth of MM cells-induced tumors.

[1]. Wang Y, et al. A Small Molecule Inhibitor Targeting TRIP13 suppresses multiple myeloma progression. Cancer Res. 2019 Nov 15. pii: canres.3987.2018.