Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute (CNCI), Kolkata 700026, India.
Molecules. 2022 Aug 15;27(16):5192. doi: 10.3390/molecules27165192.
Advancement in novel target detection using improved molecular cancer biology has opened up new avenues for promising anti-cancer drug development. In the past two decades, the mechanism of tumor hypoxia has become more understandable with the discovery of hypoxia-inducible factor-1α (HIF-1α). It is a major transcriptional regulator that coordinates the activity of various transcription factors and their downstream molecules involved in tumorigenesis. HIF-1α not only plays a crucial role in the adaptation of tumor cells to hypoxia but also regulates different biological processes, including cell proliferation, survival, cellular metabolism, angiogenesis, metastasis, cancer stem cell maintenance, and propagation. Therefore, HIF-1α overexpression is strongly associated with poor prognosis in patients with different solid cancers. Hence, pharmacological targeting of HIF-1α has been considered to be a novel cancer therapeutic strategy in recent years. In this review, we provide brief descriptions of natural and synthetic compounds as HIF-1α inhibitors that have the potential to accelerate anticancer drug discovery. This review also introduces the mode of action of these compounds for a better understanding of the chemical leads, which could be useful as cancer therapeutics in the future.
利用改良的分子癌症生物学进行新型靶标检测的进展为有前途的抗癌药物开发开辟了新途径。在过去的二十年中，随着缺氧诱导因子-1α（HIF-1α）的发现，肿瘤缺氧的机制变得更加容易理解。它是一种主要的转录调节剂，协调参与肿瘤发生的各种转录因子及其下游分子的活性。HIF-1α不仅在肿瘤细胞对缺氧的适应中起关键作用，而且还调节不同的生物学过程，包括细胞增殖、存活、细胞代谢、血管生成、转移、癌症干细胞维持和增殖。因此，不同实体瘤患者中 HIF-1α的过表达与预后不良密切相关。因此，近年来，针对 HIF-1α的药理学靶向治疗被认为是一种新的癌症治疗策略。在这篇综述中，我们简要描述了作为 HIF-1α抑制剂的天然和合成化合物，这些化合物有可能加速抗癌药物的发现。本文还介绍了这些化合物的作用模式，以便更好地了解化学先导物，这些先导物将来可能对癌症治疗有用。
