TCPs: Privileged Scaffolds for Identifying Potent LSD1 Inhibitors for Cancer Therapy

Abstract

Since the first lysine-specific demethylase (KDM), lysine-specific demethylase 1 (LSD1), was characterized in 2004, several families of KDMs have been identified. LSD1 can specifically demethylate H3K4me1/2, H3K9me1/2 as well as some nonhistone substrates. It has been demonstrated to be an oncogene as well as a drug target. Hence, tens of small-molecule LSD1 inhibitors have been designed, synthesized and applied for cancer treatment. However, the two LSD1 inhibitors that have been advanced into early phase clinical trials are trans-2-phenylcyclopropylamine (TCP) derivatives, which indicate that TCP is a druggable scaffold for LSD1 inhibitor. Here, we review the design, synthesis and properties of reported TCP-based LSD1 inhibitors as well as their biological roles.

Keywords::

• cancer
• inhibitor
• LSD1
• trans-2-phenylcyclopropylamine

Acknowledgements

The authors thank B Omolo (Stop & Shop Pharmacy, New Jersey, USA) for editing the article.

Financial & competing interests disclosure

This work was supported by National Natural Science Foundation of China (Project No. 81430085, No. 21372206 and No. 81172937 for H-M Liu); PhD Educational Award from Ministry of Education (No. 20134101130001, for H-M Liu); The 2013 Young Teacher Foundation from Zhengzhou University (No. 000001307615, for Y-C Zheng); Key Scientific Research Project for Higher Education by Department of Education of Henan Province (No. 15A350018, for Y-C Zheng). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (Project No. 81430085, No. 21372206 and No. 81172937 for H-M Liu); PhD Educational Award from Ministry of Education (No. 20134101130001, for H-M Liu); The 2013 Young Teacher Foundation from Zhengzhou University (No. 000001307615, for Y-C Zheng); Key Scientific Research Project for Higher Education by Department of Education of Henan Province (No. 15A350018, for Y-C Zheng). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.