Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), is a cysteine protease that promotes SUMO maturation and deSUMOylation of target proteins and regulates transcription factors or co-regulatory factors to mediate gene transcription. Many studies have shown that SENP1 is the driving factor for a multitude of cancers including prostate cancer, liver cancer, and breast cancer. Inhibition of SENP1 activity has been proved to inhibit the survival, proliferation, invasion, and migration of cancer cells, and increase their chemical and radiation sensitivity. Therefore, SENP1 is a promising anti-tumor target. At present, peptide inhibitors of SENP1 have entered clinical trials. Recently, many small molecule compounds and natural products were synthesized and identified as SENP1 inhibitors, and showed good tumor inhibitory activity in vitro and in vivo. This review summarizes the structure, physiological function, and role of SENP1 in tumorigenesis and development, focusing on the design and discovery of small molecule inhibitors of SENP1 from the perspective of medicinal chemistry, providing ideas for the development and research of small molecule inhibitors of SENP1 in the future.

Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1)，是一种半胱氨酸蛋白酶，可促进目标蛋白的 SUMO 成熟和去SUMOylation，并通过调节转录因子或共调节因子介导基因转录。许多研究表明，SENP1 是多种癌症的驱动因素，包括前列腺癌、肝癌和乳腺癌。已证明抑制 SENP1 活性可抑制癌细胞的存活、增殖、侵袭和迁移，并增加其化学和辐射敏感性。因此，SENP1 是一个很有前景的抗肿瘤靶点。目前，SENP1的肽抑制剂已进入临床试验。近年来，合成了许多小分子化合物和天然产物并鉴定为SENP1抑制剂，并显示出良好的肿瘤抑制活性。体外和体内。本文综述了SENP1的结构、生理功能及在肿瘤发生发展中的作用，重点从药物化学的角度设计和发现SENP1小分子抑制剂，为SENP1小分子抑制剂的开发和研究提供思路。在将来。