Zhao Hongyu, Serby Michael D, Xin Zhili, Szczepankiewicz Bruce G, Liu Mei, Kosogof Christi, Liu Bo, Nelson Lissa T J, Johnson Eric F, Wang Sanyi, Pederson Terry, Gum Rebecca J, Clampit Jill E, Haasch Deanna L, Abad-Zapatero Cele, Fry Elizabeth H, Rondinone Cristina, Trevillyan James M, Sham Hing L, Liu Gang
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6098, USA.
J Med Chem. 2006 Jul 27;49(15):4455-8. doi: 10.1021/jm060465l.
C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of inhibiting these enzymes and as leads for potential drugs targeting JNKs. In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles.
c-Jun氨基末端激酶（JNKs）是重要的细胞信号传导酶。JNK1在连接肥胖与胰岛素抵抗方面起核心作用。JNK2和JNK3可能分别参与炎症和神经疾病。小分子JNK抑制剂可能是研究抑制这些酶的治疗益处的有价值工具，并且可作为靶向JNKs的潜在药物先导物。在本报告中，我们披露了一系列具有良好药代动力学特征的强效且高度选择性的JNK抑制剂。
