膦酸酯衍生物作为自分泌运动因子（ATX）抑制剂的合成及生物学评价
Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors.
作者信息
Cui Peng, Tomsig Jose L, McCalmont William F, Lee Sangderk, Becker Christopher J, Lynch Kevin R, Macdonald Timothy L
机构信息
Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, VA 22904, USA.
出版信息
Bioorg Med Chem Lett. 2007 Mar 15;17(6):1634-40. doi: 10.1016/j.bmcl.2006.12.114. Epub 2007 Jan 13.
Abstract
Autotaxin (ATX) is an autocrine motility factor that promotes cancer cell invasion, cell migration, and angiogenesis. ATX, originally discovered as a nucleotide phosphodiesterase, is known now to be responsible for the lysophospholipid-preferring phospholipase D activity in plasma. As such, it catalyzes the production of lysophosphatidic acid (LPA) from lysophophatidylcholine (LPC). ATX is thus an attractive drug target; small molecular inhibitors might be efficacious in slowing the spread of cancers. With this study we have generated a series of beta-keto and beta-hydroxy phosphonate derivatives of LPA, some of which are potent ATX inhibitors.
摘要
自分泌运动因子（ATX）是一种自分泌运动因子，可促进癌细胞侵袭、细胞迁移和血管生成。ATX最初被发现是一种核苷酸磷酸二酯酶，现在已知它负责血浆中偏好溶血磷脂的磷脂酶D活性。因此，它催化溶血磷脂酰胆碱（LPC）生成溶血磷脂酸（LPA）。因此，ATX是一个有吸引力的药物靶点；小分子抑制剂可能对减缓癌症扩散有效。通过这项研究，我们合成了一系列LPA的β-酮和β-羟基膦酸酯衍生物，其中一些是有效的ATX抑制剂。
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