Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review

Jia Jing; Li Rui; Sun Junyuan; Yang Jinfeng; Hong Zhihao; Lu Weiguo; Jia Zhenyu

doi:10.3389/fphar.2023.1122008

Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review

Front Pharmacol. 2023 Apr 5:14:1122008. doi: 10.3389/fphar.2023.1122008. eCollection 2023.

Authors

Jia Jing¹, Li Rui², Sun Junyuan¹, Yang Jinfeng³, Hong Zhihao³, Lu Weiguo^{2

4}, Jia Zhenyu⁵

Affiliations

¹ Schools of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, Zhejiang Province, China.
² Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
³ School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang Province, China.
⁴ Key Laboratory of Women's Reproductive Health Research of Zhejiang Province, Hangzhou, Zhejiang Province, China.
⁵ Institute of Occupation Diseases, Hangzhou Medical College, Hangzhou, Zhejiang Province, China.

Abstract

S-phase kinase-associated protein 2 (Skp2) is a substrate-specific adaptor in Skp1-CUL1-ROC1-F-box E3 ubiquitin ligases and widely regarded as an oncogene. Therefore, Skp2 has remained as an active anticancer research topic since its discovery. Accordingly, the structure of Skp2 has been solved and numerous Skp2 inhibiting compounds have been identified. In this review, we would describe the structural features of Skp2, introduce the ubiquitination function of SCF^Skp2, and summarize the diverse natural and synthetic Skp2 inhibiting compounds reported to date. The IC₅₀ data of the Skp2 inhibitors or inhibiting compounds in various kinds of tumors at cellular levels implied that the cancer type, stage and pathological mechanisms should be taken into consideration when selecting Skp2-inhibiting compound for cancer treatment.

Keywords: E3 ubiquitin ligase; S-phase kinase-associated protein 2; SCFSkp2; cancer treatment; inhibitor.

Publication types

Review

Grants and funding

This study was supported by the National Natural Science Foundation of China (81802622), the Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China, and the Key Laboratory of Women′s Reproductive Health Research of Zhejiang Province, Hangzhou, Zhejiang Province, China (ZDFY2020-RH-0001). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.