Medicinal Chemistry Insights in the Discovery of Novel LSD1 Inhibitors

Abstract

LSD1 is an epigenetic modulator associated with transcriptional regulation of genes involved in a broad spectrum of key cellular processes, and its activity is often altered under pathological conditions. LSD1 inhibitors are considered to be candidates for therapy of cancer, viral diseases and neurodegeneration. Many LSD1 inhibitors with various scaffolds have been disclosed, and a few potent molecules are in different stages of clinical development. In this review, we summarize recent biological findings on the roles of LSD1 and the current understanding of the clinical significance of LSD1, and focus on the medicinal chemistry strategies used in the design and development of LSD1 inhibitors as drug-like epigenetic modulators since 2012, including a brief consideration of structure–activity relationships.

Keywords::

• drug design
• epigenomics
• histone modification
• LSD1
• medicinal chemistry

Financial & competing interests disclosure

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (no. 81573347), the Science and Technology Development Project of Shandong Province (no. 2014GSF118012), Postdoctoral Fellow Allowance (ID no. P12418) from Japan Society for the Promotion of Science (JSPS), JST CREST program, Takeda Science Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Scientific Research from JSPS, the Tokyo Biochemical Research Foundation (T Suzuki), and the Uehara Memorial Foundation (T Suzuki). 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

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (no. 81573347), the Science and Technology Development Project of Shandong Province (no. 2014GSF118012), Postdoctoral Fellow Allowance (ID no. P12418) from Japan Society for the Promotion of Science (JSPS), JST CREST program, Takeda Science Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Scientific Research from JSPS, the Tokyo Biochemical Research Foundation (T Suzuki), and the Uehara Memorial Foundation (T Suzuki). 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.