DCZ0415

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

DCZ0415 在体外、体内和耐药骨髓瘤患者的原代细胞中诱导抗骨髓瘤活性。 DCZ0415 是一种有效的 TRIP13 抑制剂，可以损害非同源末端连接的修复并抑制 NF-κB 活性。DCZ0415（10、20 μM；72 小时）显示集落形成显着减少，表明它抑制细胞增殖。

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.?

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 hoursResult: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.

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.

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Others

Other Targets

TRIP13

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2242470-43-3

356.42

C23H20N2O2

>98% (HPLC)

DMSO:62.5 mg/mL (175.35 mM; Need ultrasonic)

O=C1N(C2=CC=C(CC3=CC=NC=C3)C=C2)C(C4C5C(C6)C6C(C=C5)C14)=O

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(-20℃)

With Ice Pack

≥ 2 years