Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medicial School, University of South China, Hengyang, Hunan 421001, China.
The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Bioorg Chem. 2023 Apr;133:106400. doi: 10.1016/j.bioorg.2023.106400. Epub 2023 Jan 30.
Generally, hypoxia-inducible factor-1α (HIF-1α) is highly expressed in solid tumors, it plays a key role in the occurrence and development of tumors, hindering cancer treatment in various ways. The antitumor activity and pharmacological mechanism of YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1‑benzyl indazole], an HIF-1α inhibitor, and the design and synthesis of its derivatives have attracted tremendous attention in the field of antitumor research. YC-1 is a potential drug candidate and a lead compound for tumor therapy. Hence, the multifaceted mechanism of action of YC-1 and the structure activity relationship (SAR) of its derivatives are important factors to be considered for the development of HIF-1α inhibitors. Therefore, this review aimed to provide a comprehensive overview of the various antitumor mechanisms of YC-1 in antitumor research and an in-depth summary of the SAR for the development of its derivatives. A full understanding and discussion of these aspects are expected to provide potential ideas for developing novel HIF-1α inhibitors and antitumor drugs belonging to the YC-1 class. The review also highlighted the application prospects of the YC-1 class of potential antitumor candidates, and provided some unique insights about these antitumor agents.
一般来说，缺氧诱导因子-1α（HIF-1α）在实体瘤中高度表达，它在肿瘤的发生和发展中起着关键作用，以各种方式阻碍癌症治疗。YC-1（3-（5'-羟甲基-2'-呋喃基）-1-苄基吲唑）是一种 HIF-1α抑制剂，其抗肿瘤活性和药理学机制及其衍生物的设计和合成在抗肿瘤研究领域引起了极大的关注。YC-1是一种有潜力的药物候选物和肿瘤治疗的先导化合物。因此，YC-1的多方面作用机制及其衍生物的构效关系（SAR）是开发 HIF-1α抑制剂的重要考虑因素。因此，本综述旨在全面概述 YC-1 在抗肿瘤研究中的各种抗肿瘤机制，并深入总结其衍生物的 SAR。全面理解和讨论这些方面有望为开发新型 HIF-1α抑制剂和属于 YC-1 类的抗肿瘤药物提供潜在思路。该综述还强调了 YC-1 类潜在抗肿瘤候选物的应用前景，并对这些抗肿瘤药物提供了一些独特的见解。
