Basic Science Program, Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21701, USA.
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Molecules. 2020 Dec 2;25(23):5683. doi: 10.3390/molecules25235683.
Due to its antiangiogenic and anti-immunomodulatory activity, thalidomide continues to be of clinical interest despite its teratogenic actions, and efforts to synthesize safer, clinically active thalidomide analogs are continually underway. In this study, a cohort of 27 chemically diverse thalidomide analogs was evaluated for antiangiogenic activity in an ex vivo rat aorta ring assay. The protein cereblon has been identified as the target for thalidomide, and in silico pharmacophore analysis and molecular docking with a crystal structure of human cereblon were used to investigate the cereblon binding abilities of the thalidomide analogs. The results suggest that not all antiangiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.
尽管沙利度胺具有致畸作用，但由于其抗血管生成和免疫调节活性，它仍然具有临床意义，并且人们一直在努力合成更安全、更具临床活性的沙利度胺类似物。在这项研究中，一组 27 种化学多样性的沙利度胺类似物在体外大鼠主动脉环测定中进行了抗血管生成活性评估。蛋白 cereblon 已被确定为沙利度胺的靶标，通过计算机药物化学分析和与人类 cereblon 的晶体结构的分子对接，研究了沙利度胺类似物与 cereblon 的结合能力。结果表明，并非所有具有抗血管生成作用的沙利度胺类似物都能与 cereblon 结合，可能涉及多个靶标和作用机制。
