Brantley Scott J, Cotten Steven W, Lamson David R, Smith Ginger R, Liu Rihe, Williams Kevin P
Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Biomanufacturing Research Institute and Technology Enterprise, Durham, NC 27707, USA.
Biochem Biophys Res Commun. 2017 Sep 23;491(3):773-779. doi: 10.1016/j.bbrc.2017.07.100. Epub 2017 Jul 18.
C. elegans has been widely used as a model organism for programmed cell death and apoptosis. Although the CED-3 caspase is the primary effector of cell death in C. elegans, no selective inhibitors have been identified. Utilizing high-throughput screening with recombinant C. elegans CED-3 protein, we have discovered and confirmed 21 novel small molecule inhibitors. Six compounds had IC values < 10 μM. From these, four distinct chemotypes were identified. The inhibitor scaffolds described here could lead to the development of selective molecular probes to facilitate our understanding of programmed cell death in this model organism.
秀丽隐杆线虫已被广泛用作程序性细胞死亡和细胞凋亡的模式生物。尽管CED-3半胱天冬酶是秀丽隐杆线虫细胞死亡的主要效应因子，但尚未鉴定出选择性抑制剂。利用重组秀丽隐杆线虫CED-3蛋白进行高通量筛选，我们发现并确认了21种新型小分子抑制剂。六种化合物的IC值<10μM。从中鉴定出四种不同的化学类型。本文所述的抑制剂支架可能会促进选择性分子探针的开发，以帮助我们了解这种模式生物中的程序性细胞死亡。
