Department of Pharmacology and ‡Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, USA.
J Med Chem. 2013 Mar 28;56(6):2695-9. doi: 10.1021/jm301782e. Epub 2013 Mar 13.
An iterative parallel synthesis effort identified a PLD2 selective inhibitor, ML298 (PLD1 IC50 > 20000 nM, PLD2 IC50 = 355 nM) and a dual PLD1/2 inhibitor, ML299 (PLD1 IC50 = 6 nM, PLD2 IC50 = 20 nM). SAR studies revealed that a small structural change (incorporation of a methyl group) increased PLD1 activity within this classically PLD2-preferring core and that the effect was enantiospecific. Both probes decreased invasive migration in U87-MG glioblastoma cells.
一项迭代平行合成工作鉴定出 PLD2 选择性抑制剂 ML298（PLD1 IC50＞20000 nM，PLD2 IC50 = 355 nM）和双 PLD1/2 抑制剂 ML299（PLD1 IC50 = 6 nM，PLD2 IC50 = 20 nM）。SAR 研究表明，此类结构中，一个微小的结构变化（引入一个甲基）增加了 PLD1 的活性，而这种影响是对映体特异性的。这两种探针都降低了 U87-MG 神经胶质瘤细胞的侵袭性迁移。
