QNZ

QNZ (EVP4593) shows strong inhibitory effects on NF-κB transcriptional activation and TNF-α production with IC₅₀s of 11 and 7 nM, respectively. QNZ (EVP4593) is a neuroprotective inhibitor of SOC channel. IC50 & Target: IC50: 7 nM (TNF-α), 11 nM (NF-κB)^[1]
SOC Channel^[2] In Vitro: QNZ (Compound 11q) has a suppressing effect of the NF-κB mediated-inflammatory response. QNZ inhibits edema formation dose-dependently^[1]. QNZ (EVP4593) reduces the number of lysosomes/autophagosomes and store-operated channel (SOC) currents in Huntington's disease (HD). Normalization of calcium transport within neurons in response to QNZ is expect to reduce pathology manifestation. A number of lysosomes/autophagosomes are evaluated in HD and WT neurons treated with QNZ using transmission electron microscopy (TEM). Incubation with QNZ reduces the number of lysosomes/autophagosomes in HD GABAergic medium spiny (GABA MS)-like neurons (GMSLNs) by almost two-fold (from 0.41±0.04 to 0.23±0.04; p<0.05), while WT neurons are not affected. This observation is confirmed by examining lysosome content by flow cytometry (FC) analysis. The median fluorescence intensity is reduced by 34±6 % in HD GMSLNs upon QNZ treatment (p<0.05)^[2].