DCZ0415 在体外、体内和耐药性骨髓瘤患者的原代细胞中诱导抗骨髓瘤活性。它是一种 TRIP13 抑制剂，可损害非同源末端连接的修复并抑制 NF-Κb 活性。

DCZ0415 induces antimyeloma activity in vitro, in vivo and in primary cells of drug-resistant myeloma patients. DCZ0415 is a potent TRIP13 inhibitor that can impair the repair of non-homologous end junctions and inhibit NF-κB activity.

DCZ0415 (10, 20 μM; 72 hours) showed a marked reduction in colony formation, indicating that it inhibited cell proliferation. DCZ0415 (1.25-40 μM; 72 hours) caused a significant dose-dependent reduction in MM cell viability. DCZ0415 (10, 20 μM; 24-72 hours) showed a dose-dependent relationship between DCZ0415 treatment and apoptotic cell death. DCZ0415 (10, 20 μM; 24 hours) induced massive accumulation in G0 / G1 MM cells. DCZ0415 (10 μM; 48 hours) can reduce the protein levels of phosphorylated (p) -iκBα and phosphorylated (p) -NF-κB in MM cells. The IC50 of DCZ0415 in CalcuSyn in MM cell line is 1.0–10 μM. DCZ0415 exerts a cytotoxic effect by inhibiting the synthesis of DNA 288 in MM cells.

DCZ0415, was confirmed to bind TRIP13 using pull-down, nuclear magnetic resonance spectroscopy, and surface plasmon resonance-binding assays.?DCZ0415 induced antimyeloma activity in vitro, in vivo, and in primary cells derived from drug-resistant patients with myeloma.?The inhibitor impaired nonhomologous end joining repair and inhibited NF-κB activity.?Moreover, combining DCZ0415 with the multiple myeloma chemotherapeutic melphalan or the HDAC inhibitor panobinostat induced synergistic antimyeloma activity.?Therefore, targeting TRIP13 may be an effective therapeutic strategy for multiple myeloma, particularly refractory or relapsed multiple myeloma.

2242470-43-3

C23H20N2O2

356.42

DMSO:62.5 mg/mL (175.35 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years