IMD-0354

A potent, selective IKKβ inhibitor that inhibits NF-κB activity both in vitro and in vivo; suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors; also suppresses the growth of human breast cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing apoptosis. (In Vitro) :IMD-0354 inhibits NF-κB activity in HMC-1 cells, resulting in complete repression of growth factor-independent proliferation of mast cells. When the DNA-binding activity of NF-κB is inhibited by treatment with IMD-0354, cell proliferation is completely suppressed. HMC-1 cells are incubated with increasing concentrations of IMD-0354 or STI571 for 24, 48, and 72 hours, and numbers and viability of cells are determined by a dye exclusion test and an MTT assay. IMD-0354 suppresses cell proliferation in a time- and dose-dependent manner. The inhibitory effect of IMD-0354 is remarkable, even at lower concentrations, when compared with that of STI571. IMD0354 inhibits TNF-α induced NF-κB transcription activity with an IC50 of 1.2±0.3 uM. (In Vivo) :Daily administration with 5 mg/kg IMD-0354 significantly suppresses tumor expansion in nude mice implanted with established MDA-MB-231 tumors. In mice treated with IMD-0354, tumor progression is restrained. The number of infiltrating cells in aqueous humor is 53.6±9.8x105, 72.5±17.0x105, 127.25±32.0x105, and 132.0±25.0x105 cells/mL in rats treated with 30, 10, 3, or 0 mg/kg of IMD-0354, respectively. The total protein concentrations of aqueous humor are 92.6±3.1 mg/mL, 101.5±6.8 mg/mL, 112.6±1.9 mg/mL, and 117.33±1.8 mg/mL in rats treated with 30, 10, 3, and 0 mg/kg of IMD-0354, respectively.

978-62-1

IMD 0354 | IMD0354

>98% (HPLC)

100 mM in DMSO; 100 mM in Ethanol

O=C (NC1=CC (C (F) (F) F) =CC (C (F) (F) F) =C1) C2=CC (Cl) =CC=C2O

C15H8ClF6NO2

383.6729

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.