Salinas Yazmin, Chauhan Subhash C, Bandyopadhyay Debasish
School of Integrative Biological and Chemical Sciences, The University of Texas Rio Grande Valley, 1201 West University Drive, Edinburg, TX 78539, USA.
Division of Cancer Immunology and Microbiology, Medicine, and Oncology Integrated Service Unit, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA.
Int J Mol Sci. 2025 Apr 1;26(7):3279. doi: 10.3390/ijms26073279.
Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease's impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying chemistry, and mechanism(s) of action. The binding/inhibition of microtubule-related proteins, DNA damage through the inhibition of Checkpoint Kinase 1 protein, and the inhibition of mitotic kinase proteins are discussed in terms of their anticancer activity to provide an overview of a variety of mitotic inhibitors currently commercially available or under investigation, including those in ongoing clinical trial. Clinical trials for anti-mitotic agents are discussed to track research progress, gauge current understanding, and identify possible future prospects. Additionally, antibody-drug conjugates that use mitotic inhibitors as cytotoxic payloads are discussed as possible ways of administering effective anticancer treatments with minimal toxicity.
尽管经过了数十年的研究，癌症仍然是全球数百万人极为关注的疾病。仅在2023年，美国就有609,820人死于癌症。多年来，人们研发了许多药物来消除或减轻这种疾病的影响，这些药物的作用机制和副作用各不相同。其中一类药物是小分子有丝分裂抑制剂。这些药物抑制癌细胞的有丝分裂或自我复制，阻碍细胞增殖并最终导致细胞死亡。本文通过小分子有丝分裂抑制剂的发现、基础化学以及作用机制对其进行了讨论和分类。从它们的抗癌活性方面讨论了与微管相关蛋白的结合/抑制、通过抑制检查点激酶1蛋白导致的DNA损伤以及对有丝分裂激酶蛋白的抑制，以概述目前市面上已有的或正在研究的各种有丝分裂抑制剂，包括那些正在进行临床试验的抑制剂。讨论了抗有丝分裂药物的临床试验，以跟踪研究进展、评估当前的认知水平并确定未来可能的前景。此外，还讨论了以有丝分裂抑制剂作为细胞毒性有效载荷的抗体-药物偶联物，将其作为以最小毒性进行有效抗癌治疗的可能方式。
