LY2409881

Cell experiment:

OCI-Ly1, OCI-Ly7, and Su-DHL4 are GCB DLBCL cell lines; OCI-Ly3, OCI-Ly10, HBL1, and Su-DHL2 are ABC DLBCL lines. These cell lines are grown in Iscove Modified Dulbecco Medium with 10% FCS. Fresh medium is added every 2 to 3 days, and the cells are kept at a cell concentration of 0.1 to 1×106/mL. Cytotoxicity is evaluated using the CellTiter-Glo Reagent. Experiments are carried out in 96-well plates, with each treatment in triplicate. Samples are taken at typically 24, 48, and 72 hours after treatment. Cytotoxicity is expressed by the decreasing percentage of live cells in each treatment (LY2409881; 0.01, 0.1, 1 and 10 μM) relative to the untreated control from the same experiment, as a function of time. IC50 for each cell line is calculated using the CalcuSyn Version 2.0 software[1].

Animal experiment:

Mice[1]Mouse experiments are carried out. Five- to 7-week-old SCID beige mice are injected with 107 Ly10 cells mixed in Matrigel in the posterior flank subcutaneously. When the tumors approach 150 mm3, the mice are divided into four groups of 8 mice: (i) control group, which receive 5% dextrose in water; (ii) LY2409881 at 50 mg/kg in D5W; (iii) LY2409881 at 100 mg/kg in D5W; and (iv) LY2409881 at 200 mg/kg in D5W. LY2409881 or D5W is administered intraperitoneally on day 1 and 4 of every week for 4 weeks. The data are expressed as average tumor volume (mm3) per group as a function of time. Tumor volume is calculated.

References:

[1]. Deng C, et al. The novel IKK2 inhibitor LY2409881 potently synergizes with histone deacetylase inhibitors in preclinical models of lymphoma through the downregulation of NF-κB. Clin Cancer Res. 2015 Jan 1;21(1):134-45.