Drug Discovery Department, Research & Development Division, PharmaDesign, Inc., 2-19-8 Hatchobori, Chuo-ku, Tokyo 104-0032, Japan.
Bioorg Med Chem. 2010 Apr 1;18(7):2728-34. doi: 10.1016/j.bmc.2010.02.018. Epub 2010 Feb 15.
Death-associated protein kinase (DAPK) is a serine/threonine protein kinase implicated in diverse programmed cell death pathways. DAPK is a promising target protein for the treatment of ischemic diseases. We identified novel potent and selective DAPK inhibitors efficiently by structure-based virtual screening, then further developed the hit compounds. In this paper, we describe the development of the hit compounds and the structure-activity relationship studies of the DAPK inhibitors in detail, including calculation of the solvated interaction energy (SIE), and verification of selectivity using a kinase panel.
死亡相关蛋白激酶（DAPK）是一种丝氨酸/苏氨酸蛋白激酶，参与多种程序性细胞死亡途径。DAPK 是治疗缺血性疾病有前途的靶蛋白。我们通过基于结构的虚拟筛选有效地鉴定了新型有效的、选择性的 DAPK 抑制剂，然后进一步开发了这些命中化合物。在本文中，我们详细描述了命中化合物的开发以及 DAPK 抑制剂的结构-活性关系研究，包括溶剂化相互作用能（SIE）的计算，以及使用激酶谱进行选择性验证。
