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.
IC50&Target
NF-κB
体外研究
DCZ0415 (10, 20 μM; 72 hours) shows a significant decrease in colony formation, indicating it inhibits cell proliferation.
DCZ0415 (1.25-40 μM; 72 hours) induces a significant dose-dependent decrease of viability in
MM cells.
DCZ0415 (10, 20 μM; 24-72 hours) shows a dose-dependent relationship between DCZ0415 treatment and apoptotic cell death.
DCZ0415 (10, 20 μM; 24 hours) induces a significant accumulation in G0/G1 MM cells.
DCZ0415 (10 μM; 48 hours) decreases the protein levels of phosphorylated (p)-iκBα and phosphorylated (p)-NF-κB in MM cells.
DCZ0415 has IC50s of 1.0–10 μM in CalcuSyn in MM cell lines.
DCZ0415 exerts cytotoxic effects by inhibiting DNA 288 synthesis in MM cells.
Cell Proliferation Assay
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
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
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
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
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.
体内研究
DCZ0415 (ip; 50 mg/kg/day for 14 days) significantly reduces the growth of MM cells-induced tumors in immune-deficient mice.
Animal Model:
Nude mice (6-weeks-old) with H929 775 cells
Dosage:
50 mg/kg
Administration:
Intraperitoneal injection; every day for 14 days
Result:
Significantly reduced the growth of MM cells-induced tumors.
分子式
C23H20N2O2
分子量
356.42
CAS号
2242470-43-3
运输条件
Room temperature in continental US; may vary elsewhere.