Recent research and development of inhibitors targeting sentrin-specific protease 1 for the treatment of cancers

Abstract

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.

Keywords: Cancer treatment; SENP1; SUMO; Small-molecular inhibitors; Structure-activity relationship.