QNZ (EVP4593)

EVP4593 inhibits TNF-a production from murine splenocytes stimulated with LPS with IC50 of 7 nM. ^[1]

EVP4593 (300 nM) entails a significant decrease of amplitude of store-operated currents (approximately by 60%), induced by application of 1 μM thapsigargin in Htt138Q cells, thus prevents abnormal store-operated calcium entry. EVP4593 is able to inhibit the activity of channels containing TRPC1 as one of the subunits, but has no effect on homooligomer channels composed exclusively of TRPC1. ^[2]

QNZ (40 nM) completely abolishes the enhancement of neurite number and length evoked by laminin treatment of the schwann cells. QNZ reduces the neurite length by 61.36% of the schwann cells. QNZ significantly inhibits laminin-induced neurite outgrowth. QNZ also greatly diminishes the neurite elongation after 72 hours culture implying that both initial sprouting and longer term growth and extension seen in response to schwann cells seeded on laminin is mediated by NF-κB. ^[3]

QNZ (10 nM) abolishes LPS-induced up-regulation of CSE expression in rat neutrophil. ^[4]

QNZ (100 nM) blocks the induction effects of GRO/KC on K currents in IB4-negative neurons. ^[5]

EVP4593 (1 mg/kg, i.p.) dose-dependently inhibits carrageenin-induced paw edema in rats. ^[1]

• NF-κB assay

  Human Jurkat T cells are cultured at 37℃ in a 5% CO2 atmosphere in RPMI1640 containing 10% FCS. The cells are plated in 6-well plates (2×10⁶/well) and transiently transfected using the SuperFect Transfection Reagent with 1 μg of pNFκB-Luc. After transfection, the cells are cultured at 37℃ overnight. They are then collected, resuspended in fresh medium, and plated in 96-well plates (2×10⁵/well). EVP4593 is dissolved in DMSO and added at the appropriate concentrations to the 96-well plates containing the cells, and the plates are then incubated at 37℃ for 1 hour. For induction of transcription, 10 ng/mL of PMA and 100 μg/mL of PHA are added to each well, and the cells are incubated for an additional 6 hours at 37℃. The culture media are removed, and cell lysis buffer containing luciferase substrate is added to each well. The each portion is transferred to a black 96-well plate, and then luminescence is immediately measured with a Packard Topcount. The 50% inhibitory concentration (IC50) values are calculated by a nonlinear regression method.

• Cell lines

  Jurkat cells

• Concentrations

  IC50 of 11 nM (NF-κB) and 7 nM (TNF-α)

• Incubation Time

  1 h

• Method

  Test compounds were dissolved in DMSO and added at the appropriate concentrations to the 96-well plates containing the cells, and the plates were then incubated at 37 C for 1 h

• Animal Models

  male SD rats with carrageenin induced paw edema

• Dosages

  1 mg/kg

• Administration

  intraperitoneal injection