Laboratoire d'Innovation Thérapeutique, UMR 7200 CNRS-Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67400 Illkirch, France.
Bioorg Med Chem Lett. 2011 Jul 1;21(13):3939-42. doi: 10.1016/j.bmcl.2011.05.022. Epub 2011 May 14.
CD38 is a multifunctional enzyme which is ubiquitously distributed in mammalian tissues. It is involved in the conversion of NAD(P)(+) into cyclic ADP-ribose, NAADP(+) and ADP-ribose and the role of these metabolites in multiple Ca(2+) signaling pathways makes CD38 a novel potential pharmacological target. The dire paucity of CD38 inhibitors, however, renders the search for new molecular tools highly desirable. We report that human CD38 is inhibited at low micromolar concentrations by flavonoids such as luteolinidin, kuromanin and luteolin (IC(50) <10 μM). Docking studies provide some clues on the mode of interaction of these molecules with the active site of CD38.
CD38 是一种多功能酶，广泛分布于哺乳动物组织中。它参与 NAD(P)(+)向环 ADP-核糖、NAADP(+)和 ADP-核糖的转化，这些代谢物在多种 Ca(2+)信号通路中的作用使 CD38 成为一个新的潜在的药理学靶点。然而，CD38 抑制剂严重缺乏，这使得寻找新的分子工具变得非常迫切。我们报告说，类黄酮如 luteolinidin、kuromanin 和 luteolin 以低微摩尔浓度抑制人 CD38（IC(50)<10 μM）。对接研究为这些分子与 CD38 活性位点相互作用的模式提供了一些线索。
