6-Amino-4-(4-phenoxyphenylethylamino)quinazoline

QNZ (545380-34-5) was originally described as a potent inhibitor of NF-κB activation (IC50= 11 nM) and TNF-αproduction (IC50= 7 nM).1,2It indirectly inhibits the NF-κB pathway via inhibition of store-operated calcium entry (SOC) and displayed neuroprotective effects in transgenic fly and mouse models of Huntington’s disease.3,4Its target has been postulated to be heteromeric calcium channels containing TRPC1 as one of the subunits.4QNZ reduced synaptic neuronal SOC and rescued dendritic spine loss in YAC128 striatal medium spiny neurons.5QNZ has also been identified as a potent (IC50= 25 nM complex 1 fromY.lipolytica; IC50= 14 nM complex 1 fromBos Taurusheart mitochondria) and selective inhibitor of mitochondrial complex I.6QNZdecreased PSEN1ΔE9-mediated nSOCE upregulation and rescued mushroom spines in PSEN1ΔE9-expressing neurons, which are linked to familial Alzheimer’s disease.7

White Solid

QNZ is a novel inhibitor of NFkB which displays potent inhibitory effects on both NFKB transcriptional activation (IC50=11nM) and TNF-a production (IC50=7nM). It dose-dependently inhibited carragenin-induced edema formation in the rat paw model (1m

QNZ is an inhibitor of NF-κB activation with IC50 of 11 nM.

NF-κB

NF-κB: 11 nM (IC₅₀, in human Jurkat cells transfected with pNFκB-Luc)

[1] MASANORI TOBE. Discovery of quinazolines as a novel structural class of potent inhibitors of NF-κB activation[J]. Bioorganic & Medicinal Chemistry, 2003, 11 3: Pages 383-391. DOI:10.1016/s0968-0896(02)00440-6
[2] MASANORI TOBE. A novel structural class of potent inhibitors of NF-κB activation: structure–activity relationships and biological effects of 6-aminoquinazoline derivatives[J]. Bioorganic & Medicinal Chemistry, 2003, 11 18: Pages 3869-3878. DOI:10.1016/s0968-0896(03)00438-3
[3] SHINKYU CHOI. Nuclear factor-kappaB activated by capacitative Ca2+ entry enhances muscarinic receptor-mediated soluble amyloid precursor protein (sAPPalpha) release in SH-SY5Y cells.[J]. The Journal of Biological Chemistry, 2006, 281 18: 12722-12728. DOI:10.1074/jbc.m601018200
[4] JUN WU. Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington’s disease treatment.[J]. Chemistry & biology, 2011, 18 6: 777-793. DOI:10.1016/j.chembiol.2011.04.012
[5] JUN WU. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington’s Disease Mouse Model[J]. The Journal of Neuroscience, 2016, 196 1: 125-141. DOI:10.1523/jneurosci.1038-15.2016
[6] ROBIN KRISHNATHAS. Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I.[J]. MedChemComm, 2017: 657-661. DOI:10.1039/c6md00655h
[7] DARIA CHERNYUK . Antagonist of neuronal store-operated calcium entry exerts beneficial effects in neurons expressing PSEN1ΔE9 mutant linked to familial Alzheimer disease[J]. Neuroscience, 2019, 410: Pages 118-127. DOI:10.1016/j.neuroscience.2019.04.043