文章：

基于环丁烷的β3整合素拮抗剂的合成与生物评估：一种针对整合素用于癌症治疗的创新方法

Synthesis and Biological Evaluation of Cyclobutane-Based β3 Integrin Antagonists: A Novel Approach to Targeting Integrins for Cancer Therapy

原文发布日期：8 August 2023

DOI: 10.3390/cancers15164023

类型: Article

开放获取: 是

英文摘要：

The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.

摘要翻译： 

精氨酸-甘氨酸-天冬氨酸（RGD）结合整合素受体家族，尤其是β3亚家族，在组织发育、癌症增殖及转移扩散等多个生理过程中起着关键作用。尽管大量临床前证据表明αvβ3与αIIbβ3均为重要的抗癌靶点，但目前针对β3整合素开发的拮抗剂大多对αvβ3或αIIbβ3具有高度选择性。我们报告了一类新型拟配体β3整合素拮抗剂的设计、合成与生物学评价。该拮抗剂在保持对αvβ3高活性的同时，对αIIbβ3表现出适度亲和力，这为癌症整合素靶向治疗提供了新策略的首例证据。

原文链接：

Synthesis and Biological Evaluation of Cyclobutane-Based β3 Integrin Antagonists: A Novel Approach to Targeting Integrins for Cancer Therapy