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Drug-mediated intracellular donation of nitric oxide potently inhibits 5-lipoxygenase: a possible key to future antileukotriene therapy
Roos, Jessica; Peters, Marcus; Maucher, Isabelle V.; Kühn, Benjamin; Fettel, Jasmin; Hellmuth, Nadine; Brat, Camilla; Sommer, Benita; Urbschat, Anja; Piesche, Matthias; Vogel, Anja; Proschak, Ewgenij; Blöcher, René; Buscató, Estella; Häfner, Ann-Kathrin; Matrone, Carmela; Werz, Oliver; Heidler, Juliana; Wittig, Ilka; Angioni, Carlo; Geisslinger, Gerd; Parnham, Michael J.; Zacharowski, Kai D.; Steinhilber, Dieter; Maier, Thorsten J. (2018)Aims: 5-Lipoxygenase (5-LO) is the key enzyme of leukotriene (LT) biosynthesis and is critically involved in a number of inflammatory diseases such as arthritis, gout, bronchial asthma, atherosclerosis, and cancer. Because ...
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Michael acceptor containing drugs are a novel class of 5-lipoxygenase inhibitor targeting the surface cysteines C416 and C418
Piesche, Matthias; Maucher, Isabelle V.; Rühl, Michael; Kretschmer, Simon B.M.; Hofmann, Bettina; Kühn, Benjamin; Fettel, Jasmin; Vogel, Anja; Flügel, Karsten T.; Manolikakes, Georg; Hellmuth, Nadine; Häfner, Ann-Kathrin; Golghalyani, Vahid; Ball, Ann-Katrin; Matrone, Carmela; Geisslinger, Gerd; Parnham, Michael J.; Karas, Michael; Steinhilber, Dieter; Roos, Jessica; Maier, Thorsten J. (2017)Recently, we published that nitro-fatty acids (NFA) are potent electrophilic molecules which inhibit 5-lipoxygenase (5-LO) by interacting catalytically with cysteine residues next to a substrate entry channel. The ...