Gancia Emanuela, De Groot Marcel, Burton Brenda, Clark David E
Charles River, 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, United Kingdom.
Charles River, 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, United Kingdom.
Bioorg Med Chem Lett. 2017 Jun 1;27(11):2520-2527. doi: 10.1016/j.bmcl.2017.03.098. Epub 2017 Apr 2.
In this paper, we present the results of a ligand- and structure-based virtual screen targeting LRRK2, a kinase that has been implicated in Parkinson's disease. For the ligand-based virtual screen, the structures of 12 competitor compounds were used as queries for a variety of 2D and 3D searches. The structure-based virtual screen relied on homology models of LRRK2, as no X-ray structure is currently available in the public domain. From the virtual screening, 662 compounds were purchased, of which 35 showed IC values below 10μM in wild-type and/or mutant LRRK2 (a hit rate of 5.3%). Of these 35 hits, four were deemed to have potential for medicinal chemistry follow-up.
在本文中，我们展示了针对富亮氨酸重复激酶2（LRRK2）的基于配体和结构的虚拟筛选结果，该激酶与帕金森病有关。对于基于配体的虚拟筛选，使用12种竞争化合物的结构作为各种二维和三维搜索的查询。基于结构的虚拟筛选依赖于LRRK2的同源模型，因为目前公共领域没有X射线结构。通过虚拟筛选，购买了662种化合物，其中35种在野生型和/或突变型LRRK2中显示出低于10μM的IC值（命中率为5.3%）。在这35个命中物中，有4个被认为有进行药物化学后续研究的潜力。
