动物细胞中的中心体在纺锤体极形成、新核形成、细胞分裂期间微管的正确排列以及染色体在每个子细胞中的分布中起着关键作用。中心体扩增涉及中心体结构和数量的异常，可能导致染色体不稳定性和细胞周期失调，进而导致癌症发展和转移。然而，中心体扩增引起的干扰也可以通过激活有丝分裂检查点和促进有丝分裂灾变来限制癌细胞的生存。作为一种聪明的逃避方式，癌细胞将其过剩的中心体聚集成伪双极纺锤体并进入细胞周期。这种现象被称为中心体聚集，涉及许多蛋白质，并引起了相当大的关注，被视为一种特定的癌细胞靶向武器。Kinesin-14马达蛋白KIFC1是一种朝负端定向的马达蛋白，参与中心体聚集。由于KIFC1在各种癌症中上调并调节致癌信号级联反应，因此已被视为潜在的化疗靶点。许多分子已被确定为KIFC1抑制剂，因为它们在癌细胞中具有中心体解聚活性。尽管该领域的文献越来越多，但几乎没有人努力回顾这一进展。本综述旨在汇编并呈现已知的KIFC1抑制剂及其生物活性的深入分析。此外，我们呈现了假设的KIFC1抑制剂与其结合位点和结合亲和力的计算对接数据。这种首次进行实验生物学、化学和不同KIFC1抑制剂的计算对接的比较分析可能有助于指导在选择和设计有效的抑制剂方面的决策。© 2022 Wiley Periodicals LLC.

The centrosome in animal cells is instrumental in spindle pole formation, nucleation, proper alignment of microtubules during cell division, and distribution of chromosomes in each daughter cell. Centrosome amplification involving structural and numerical abnormalities in the centrosome can cause chromosomal instability and dysregulation of the cell cycle, leading to cancer development and metastasis. However, disturbances caused by centrosome amplification can also limit cancer cell survival by activating mitotic checkpoints and promoting mitotic catastrophe. As a smart escape, cancer cells cluster their surplus of centrosomes into pseudo-bipolar spindles and progress through the cell cycle. This phenomenon, known as centrosome clustering (CC), involves many proteins and has garnered considerable attention as a specific cancer cell-targeting weapon. The kinesin-14 motor protein KIFC1 is a minus end-directed motor protein that is involved in CC. Because KIFC1 is upregulated in various cancers and modulates oncogenic signaling cascades, it has emerged as a potential chemotherapeutic target. Many molecules have been identified as KIFC1 inhibitors because of their centrosome declustering activity in cancer cells. Despite the ever-increasing literature in this field, there have been few efforts to review the progress. The current review aims to collate and present an in-depth analysis of known KIFC1 inhibitors and their biological activities. Additionally, we present computational docking data of putative KIFC1 inhibitors with their binding sites and binding affinities. This first-of-kind comparative analysis involving experimental biology, chemistry, and computational docking of different KIFC1 inhibitors may help guide decision-making in the selection and design of potent inhibitors.© 2022 Wiley Periodicals LLC.