DCZ0415 (DCZ-0415; DCZ 0415) is a novel and highly potent TRIP13 inhibitor that is able to impair 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.
Physicochemical Properties
| Molecular Formula | C23H20N2O2 |
| Molecular Weight | 356.4171 |
| Exact Mass | 356.15 |
| Elemental Analysis | C, 77.51; H, 5.66; N, 7.86; O, 8.98 |
| CAS # | 2242470-43-3 |
| Related CAS # | 2242470-43-3 |
| PubChem CID | 145925662 |
| Appearance | Off-white to yellow solid powder |
| LogP | 3 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 27 |
| Complexity | 638 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | LOXMLWHUIONWMI-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H20N2O2/c26-22-20-16-5-6-17(19-12-18(16)19)21(20)23(27)25(22)15-3-1-13(2-4-15)11-14-7-9-24-10-8-14/h1-10,16-21H,11-12H2 |
| Chemical Name | 4-[4-(pyridin-4-ylmethyl)phenyl]-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione |
| Synonyms | DCZ 0415; DCZ0415; DCZ-0415 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | NF-κB |
| ln Vitro |
Colony formation is significantly reduced in response to DCZ0415 (10, 20 μM; 72 hours), which suggests that it inhibits cell proliferation[1]. In MM cells, DCZ0415 (1.25–40 μM; 72 hours) causes a significant dose-dependent reduction in viability[1]. Treatment with DCZ0415 (10, 20 μM; 24-72 hours) elicits apoptotic cell death in a dose-dependent manner[1]. In G0/G1 MM cells, DCZ0415 (10, 20 μM; 24 hours) induces a sizable accumulation[1]. In MM cells, DCZ0415 (10 μM; 48 hours) reduces the levels of phosphorylated (p)-iB and phosphorylated (p)-NF-B proteins[1]. In CalcuSyn in MM cell lines, DCZ0415 has IC50 values of 1.0–10 μM[1]. In MM cells, DCZ0415 inhibits the synthesis of DNA 288 to cause cytotoxic effects[1]. |
| ln Vivo | In immune-deficient mice, DCZ0415 (ip; 50 mg/kg/day for 14 days) significantly slows the growth of tumors brought on by MM cells[1]. |
| Animal Protocol |
Nude mice (6-weeks-old) with H929 775 cells[1] 50 mg/kg Intraperitoneal injection; every day for 14 days |
| References |
[1]. A Small Molecule Inhibitor Targeting TRIP13 suppresses multiple myeloma progression. Cancer Res. 2019 Nov 15. pii: canres.3987.2018 |
Solubility Data
| Solubility (In Vitro) | DMSO: ~62.5 mg/mL (~175.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8057 mL | 14.0284 mL | 28.0568 mL | |
| 5 mM | 0.5611 mL | 2.8057 mL | 5.6114 mL | |
| 10 mM | 0.2806 mL | 1.4028 mL | 2.8057 mL |