在大多数突变p53的恶性肿瘤中，DNA损伤修复更依赖于G2/M检查点。Wee1激酶是G2/M检查点的关键调节因子。如果抑制Wee1，结果是未修复DNA损伤的细胞过早进入有丝分裂，导致有丝分裂灾难并通过凋亡程序引起细胞死亡。因此，抑制Wee1激酶已成为治疗癌症的有前途的疗法，多个癌细胞系中也过度表达Wee1激酶。本文首次总结了2003年至2022年之间发表的专利中报告的Wee1小分子抑制剂的结构及最近的临床进展，并提出了挑战和未来方向。我们使用不同的方法搜索不同的数据库（PubMed、Reaxys、临床试验网）来获取所需的文献。虽然Wee1小分子抑制剂Adavosertib和ZN-C3已进入临床II期，但Adavosertib显示出的临床毒性仍是更大的关注点。Wee1抑制剂的单一疗法或联合疗法仍是当前Wee1抑制剂的主要趋势。

DNA damage repair in most malignancies with mutation of p53 is more dependent on the G2/M checkpoint. Wee1 kinase is a key regulator of the G2/M checkpoint. If Wee1 is inhibited, it results in cells with unrepaired DNA damage entering mitosis prematurely, leading to mitotic catastrophe and subsequent cell death via the apoptotic program. Therefore, inhibition of Wee1 kinase which overexpressed in several cancer cell lines has emerged as a promising therapy for cancer treatment.This review summarizes for the first time the structures of small-molecule inhibitors of Wee1 reported in patents published from 2003 to 2022 and the recent clinical developments. It also provides perspectives on the challenges and the future directions. We used different methods to search different databases (PubMed, Reaxys, clinicaltrials.gov)for the literature we needed.Although the small-molecule inhibitors of Wee1, Adavosertib, and ZN-C3 have entered the clinical phase II, the clinical toxicity exhibited by Adavosertib remains the subject of greater concern. The use of Wee1 inhibitors as monotherapy or in combination therapy remains the main trend in Wee1 inhibitors at present.