Zileuton抑制剂、激动剂(CAS号111406-87-2)Zileuton (齐留通; A-64077) 是5-脂肪氧合酶抑制剂,能抑制白细胞三烯(LTB4,LTC4,LTD4和LTE4)的形成。 Zileuton (A-64077) is a selective and potent 5-LO inhibitor, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation.
IC50 Value:
Target: 5-lipoxygenase
in vitro: Zileuton inhibited 5-hydroxyeicosatetraenoic acid synthesis by rat basophilic leukemia cell 20,000 x g supernatant and rat polymorphonuclear leukocytes (PMNL) (IC50 = 0.5 and 0.3 microM) respectively. It also inhibited leukotriene (LT)B4 biosynthesis by rat PMNL (IC50 = 0.4 microM), human PMNL (IC50 = 0.4 microM) and human whole blood (IC50 = 0.9 microM) [1]. Zileuton inhibited antigen-induced contractions of guinea-pig tracheal strips (GPTS) from actively sensitized animals with an IC50of 6 microM [1].
in vivo: Additionally, while total tau levels were unchanged for both groups, zileuton-treated mice had a significant reduction in its phosphorylation state and insoluble forms, secondary to a decreased activation of the cdk5 kinase [2]. Neurological deficit scores, infarct volume, and neuronal damage were significantly attenuated by administration of zileuton. MCAO caused the elevation of neuronal apoptosis, which was significantly inhibited by the administration of zileuton. MCAO caused the over-expression of caspase-1 and cleaved caspase-3, both of which were significantly inhibited by the administration of zileuton [3].
Toxicity: Previous research from the authors' laboratory demonstrated the formation of the reactive metabolite, 2-ABT-S-oxide (M1) from zileuton, and has identified a mercapturate of 2-ABT, C1, in the urine of rats dosed with zileuton. The reaction between M1 and glutathione (GSH) has been established in vitro. [4]
Clinical trial: VERSE: A Study of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and A Second Controller Medication. Phase 3