Lenalidomide (CC-5013) is an immunomodulator with oral activity. Lenalidomide is a ligand for the ubiquitin E3 ligase cereblon (CRBN), which selectively ubiquitinates and degrades two lymphoid transcription factors, IKZF1 and IKZF3, via the CRBN-CRL4 ubiquitin ligase, and is commonly used in the synthesis of PROTAC products.

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METHODS: Six malignant glioma cell lines, A-172, AM-38, T98G, U-138MG, U-251MG, and YH-13, were treated with Lenalidomide (0.01-100 µM) for 72 h, and cell counts were detected by Coulter counter assay.
RESULTS: Lenalidomide inhibited cell counts of all malignant glioma cells in a concentration-dependent manner. [1]
METHODS: DCs were differentiated from BM CD14+ cells from MM patients, treated with Lenalidomide (0.1-1 µM) for 8 days and analyzed for DC maturation markers by flow-cytometry.
RESULTS: Despite a reduction in the number and percentage of mature DCs, Lenalidomide significantly increased the expression of HLA-DR, CD86, and CD209 in DCs derived from BM over the range of concentrations achieved in MM patients. [2]

METHODS: To test the antitumor activity in vivo, Lenalidomide (25 mg/kg) was injected intraperitoneally into C57BL/KaLwRij or B6-SCID mice bearing 5TGM1 tumors once daily for 21 days.
RESULTS: Lenalidomide inhibited tumor growth and prolonged survival of C57BL/KaLwRij mice bearing 5TGM1 tumors.Lenalidomide significantly increased the number of IFN-γ-secreting CD4+ and CD8+ T cells but had no effect on NK cells and B cells in the B6-SCID mouse model. Lenalidomide slightly decreased the number of CD25+Foxp3+ T cells in vivo, but increased perforin expression in CD8+ T cells.Lenalidomide promoted type 1 antitumor immune responses in vivo. [3]

The human NSCLC cell lines Lu-99, H1299, A549, EBC1, and H460 were cultured in RPMI-1640 medium containing 10% fetal bovine serum and antibiotics at 37°C in a humidified chamber containing 5% CO2. Cells were seeded into 60-mm culture dishes (2x10^5 cells per dish) with various concentrations of lenalidomide and incubated for various times [1].

Mice were administered sterile preparations of lenalidomide normalized to body weight. Intravenously (IV) dosed animals received drug by bolus tail vein injections, and extravascularly dosed mice received drug by bolus intraperitoneal injections (IP) or oral gavage (PO). Dosing solution, concentrations were adjusted so dose volumes ranged between approximately 100 and 150 μL for IV injections and between approximately 150 and 250 μL for IP and PO dosing in the pharmacokinetic study. However, for the range-finding study, increased dose volumes were used (up to 200 μL IV, 300 μL IP, and 600 μL PO, per approved animal use protocol) to explore elevated lenalidomide doses. The bolus injection rates for all IV, IP, or PO injections were less than 5 s. Concentrations of dosing solutions were verified by liquid chromatography-mass spectrometry [4].