In vitro: Y2409881 inhibited constitutively activated NF-κB, and caused concentration- and time-dependent growth inhibition and apoptosis in lymphoma cells. Pretreatment of LY10 with 10 umol/L of LY2409881 prevented the formation of phosphorylated IkB in samples treated with TNFa for 2, 20, and 60 minutes in the presence of abundant IkB protein.
In vivo: LY2409881 was safe to mice at three dose levels, 50, 100, and 200 mg/kg, all of which caused significant inhibition of tumor growth. LY2409881 suppressed the activity of the NF-κB subunit p65 in lymphoma cells treated by the HDAC inhibitor romidepsin, underlying a potential mechanism of the marked synergy observed of these two drugs.
 |
Source | Clin Cancer Res (2015). Figure 2. LY2409881 |
| Method | Vybrant Apoptosis Assay | |
| Cell Lines | SUDHL2 cells | |
| Concentrations | 10 and 20 μmol/L | |
| Incubation Time | 24 h | |
| Results | These results confirm that LY2409881 inhibits constitutively activated NF-κB, leading to cell death in B- and T-cell lymphoma cell lines. |
| Cell Experiment | |
|---|---|
| Cell lines | DLBCL cell line |
| Preparation method | After incubation with LY2409881for 4 hours, the samples were placed on the slides using the Cytospin. After fixation in 10% formalin and 100% methanol, the slides were transferred to the blocking buffer (10% nonfat dry milk) and incubated with primary antibody in the humidity chamber overnight. |
| Concentrations | 10 μmol/L |
| Incubation time | 4 h |
| Animal Experiment | |
|---|---|
| Animal models | SCID beige mice |
| Formulation | 5% dextrose in wate |
| Dosages | 50 mg/kg, 100 mg/kg, 200 mg/kg |
| Administration | i.v. |
| Molecular Weight | 485.04 |
| Formula | C24H29ClN6OS |
| CAS Number | 946518-61-2 |
| Solubility (25°C) | DMSO 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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