| Bioactivity | 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. | ||||||||||||
| Invitro | 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]. | ||||||||||||
| Name | QNZ | ||||||||||||
| CAS | 545380-34-5 | ||||||||||||
| Formula | C22H20N4O | ||||||||||||
| Molar Mass | 356.42 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Tobe M, et al. Discovery of quinazolines as a novel structural class of potent inhibitors of NF-kappa B activation. [2]. Nekrasov ED, et al. Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons. Mol Neurodegener. 2016 Apr 14;11:27. [3]. Wu J, et al. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model. J Neurosci. 2016 Jan 6;36(1):125-41. |