申请人:VIRONGY LLC
公开号:WO2017201187A1
公开(公告)日:2017-11-23
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For the human immunodeficiency virus (HIV), during viral entry, the virus triggers early actin activity through hijacking chemokine coreceptor signaling, which activates a viral dependency host factor cofilin and its kinase, the LIM domain kinase (LIMK).. Although knockdown of human LIMK1 with siRNA inhibits HIV infection, no specific small molecule inhibitor of LIMK is available. Here we describe the design and development of novel classes of small molecule inhibitors of human LIMK, based on different molecular scaffolds, for inhibiting infection by HIV, Ebola, and other viruses. Compounds of the invention can also be used for treatment of sexually transmitted diseases such as Herpes and Chlamydia.
一个动态的肌动蛋白细胞骨架对于病毒进入、细胞内迁移和病毒释放是必要的。对于人类免疫缺陷病毒(HIV),在病毒进入期间,病毒通过劫持趋化因子共受体信号传导来触发早期肌动蛋白活性,这激活了病毒依赖的宿主因子螺丝蛋白和其激酶,即LIM结构域激酶(LIMK)。尽管用siRNA敲除人类LIMK1可以抑制HIV感染,但目前没有特定的LIMK小分子抑制剂。在这里,我们描述了基于不同分子支架的人类LIMK小分子抑制剂的设计和开发,用于抑制HIV、埃博拉病毒和其他病毒的感染。本发明的化合物还可用于治疗性病,如疱疹和沙眼衣原体。