QNZ (EVP4593) is a highly potent and selective inhibitor of the nuclear factor κB (NF-κB) signaling pathway with an IC50 value of 11nM and has anti-inflammatory effects[1, 2]. QNZ (EVP4593) is a neuroprotective agent that acts by inhibiting store-operated calcium channels (SOC)[3].
In vitro, QNZ (EVP4593) (10μM) treatment of mouse fibroblasts for 48h inhibited the proliferation and migration of fibroblasts and the expression of the proliferation marker Ki67 in cells[4]. QNZ (EVP4593) (10nM) treatment of LNCap and PC-3 cells for 7 days significantly increased the sensitivity of cells to carboplatin, inhibited the phosphorylation of intracellular AKT or p65, and increased the expression of E-cadherin[5].
In vivo, QNZ (EVP4593) (1mg/kg) was administered intraperitoneally to rats with myocardial ischemia/reperfusion (I/R) injury, enhancing the cardioprotective effect induced by morphine postconditioning (MP) and attenuating myocardial ischemia/reperfusion injury[6]. QNZ (EVP4593) (1mg/kg) was administered intraperitoneally to mice bearing DLD1 cell xenografts for 14 days, enhancing the antitumor activity of bevacizumab in vivo[7].
References:
[1] Grekhnev D A, Kruchinina A A, Vigont V A, et al. The Mystery of EVP4593: Perspectives of the quinazoline-derived compound in the treatment of Huntington’s disease and other human pathologies[J]. International Journal of Molecular Sciences, 2022, 23(24): 15724.
[2] Tobe M, Isobe Y, Tomizawa H, et al. Discovery of quinazolines as a novel structural class of potent inhibitors of NF-κB activation[J]. Bioorganic & medicinal chemistry, 2003, 11(3): 383-391.
[3] Chauvet S, Jarvis L, Chevallet M, et al. Pharmacological characterization of the native store-operated calcium channels of cortical neurons from embryonic mouse brain[J]. Frontiers in pharmacology, 2016, 7: 486.
[4] Huang F, Wang H, Zhang Y, et al. Synergistic effect of QNZ, an inhibitor of NF-κB signaling, and bone morphogenetic protein 2 on osteogenic differentiation in mesenchymal stem cells through fibroblast-induced yes-associated protein activation[J]. International Journal of Molecular Sciences, 2023, 24(9): 7707.
[5] He Y, Zhang Q, Chen H, et al. Astragaloside IV enhanced carboplatin sensitivity in prostate cancer by suppressing AKT/NF-κB signaling pathway[J]. Biochemistry and Cell Biology, 2021, 99(2): 214-222.
[6] Tu R H, Wang D X, Zhong G Q, et al. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB[J]. Open Medicine, 2021, 16(1): 1552-1563.
[7] Marciano R, Prasad M, Ievy T, et al. High-throughput screening identified compounds sensitizing tumor cells to glucose starvation in culture and VEGF inhibitors in vivo[J]. Cancers, 2019, 11(2): 156.
QNZ (EVP4593)是一种高效、选择性核因子κB（NF-κB）信号通路抑制剂，IC50值为11nM，具有抗炎功效[1, 2]。QNZ (EVP4593)是一种神经保护剂，通过抑制钙池操纵的钙通道（SOC）发挥作用[3]。
在体外，QNZ (EVP4593)（10μM）处理小鼠成纤维细胞48h，抑制了成纤维细胞的增殖和迁移，抑制了细胞中增殖标志物Ki67的表达[4]。QNZ (EVP4593)（10nM）处理LNCap和PC-3细胞7天，显著提高了细胞对卡铂的敏感性，抑制了细胞内AKT或p65的磷酸化，增加了E-钙粘蛋白（E-cadherin）的表达[5]。
在体内，QNZ (EVP4593)（1mg/kg）通过腹腔注射治疗心肌缺血/再灌注（I/R） 损伤大鼠，增强了吗啡后处理（MP）诱导的心脏保护作用，减轻了心肌缺血/再灌注损伤[6]。QNZ (EVP4593)（1mg/kg）通过腹腔注射治疗DLD1细胞异种移植小鼠14天，增强了贝伐单抗在体内的抗肿瘤活性[7]。