View source for Krishnathas 2017 Med Chem Comm

{{Publication
|title=Krishnathas R, Bonke E, Dröse S, Zickermann V, Nasiri HR (2017) Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I. Med Chem Comm 8:657-61.
|info=[http://pubs.rsc.org/en/content/articlelanding/2017/md/c6md00655h#!divAbstract]
|authors=Krishnathas R, Bonke E, Droese S, Zickermann V, Nasiri HR
|year=2017
|journal=Med Chem Comm
|abstract=By probing the quinone substrate binding site of mitochondrial complex I with a focused set of
quinazoline-based compounds, we identified substitution patterns as being critical for the observed inhibition. The structure activity relationship study also resulted in the discovery of the quinazoline 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (EVP4593) as a highly potent inhibitor of the multisubunitmembrane protein. EVP4593 specifically and effectively reduces the mitochondrial complex I-dependent respiration with no effect on the respiratory chain complexes II–IV. Similar to established Q-site inhibitors, EVP4593 elicits the release of reactive oxygen species at the flavin site of mitochondrial complex I. Recently, EVP4593 was nominated as a lead compound for the treatment of Huntingtons disease. Our results challenge the postulated primary mode-of-action of EVP4593 as an inhibitor of NF-κB pathway activation and/or store-operated calcium influx.
|editor=[[Kandolf G]]
|mipnetlab=DE Frankfurt Droese S
}}
{{Labeling
|area=Respiration, Pharmacology;toxicology
|organism=Rat
|tissues=Heart
|preparations=Isolated mitochondria
|topics=Inhibitor
|couplingstates=OXPHOS
|pathways=N, S
|instruments=Oxygraph-2k
}}