Uses
A potent, reversible inhibitor of 5-lipoxygenase, blocking leukotriene synthesis with an IC50 value of 0.7 μM in intact human polymorphonuclear leukocytes. It also attenuates leukotriene B4 synthesis, prevents carrageenan-induced pleurisy, and protects against platelet-activating factor-induced shock in mice when given intraperitoneally.
Definition
ChEBI: HZ52 is a member of biphenyls.
Biological Activity
2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2- ylthio)octanoic acid (hz52) is an inhibitor for 5-lipoxygenase (5-lo) [1]. 5-lipoxygenase (5-lo), the key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes (lts), is a potential target for pharmacological intervention with inflammation and allergic disorders [1].
in vitro
in cell-free assays using partially purified recombinant 5-lo enzyme, hz52 inhibited 5-lo with an ic50 of 1.5 μm. in pmnl homogenates, hz52 inhibited 5-lo with an ic50 of 9 μm [1]. hz52 (10 or 30 μm) promoted 5-lo translocation to the nuclear membrane in pmnl [1]. the cell-based and cell-free assays revealed that inhibition of 5-lo by hz52 did not depend on radical scavenging properties and was reversible [1].
in vivo
in rats with carrageenan-induced pleurisy and in mice bearing platelet-activating factor (paf)-induced lethal shock, hz52 (1.5 mg/kg, i.p) prevented carrageenan-induced pleurisy accompanied by reducing ltb4 levels. hz52 protected mice (10 mg/kg, i.p) against paf-induced shock. [1].
References
[1] greiner c, hrnig c, rossi a, et al. 2‐(4‐(biphenyl‐4‐ylamino)‐6‐chloropyrimidin‐2‐ylthio) octanoic acid (hz52)–a novel type of 5‐lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo[j]. british journal of pharmacology, 2011, 164(2b): 781-793.
