Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors

[Display omitted] Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that c...

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Published inBioorganic & medicinal chemistry letters Vol. 41; p. 127993
Main Authors Huang, Ming-Jie, Guo, Jia-Wen, Fu, Yun-Dong, You, Ya-Zhen, Xu, Wen-Yu, Song, Ting-Yu, Li, Ran, Chen, Zi-Tong, Huang, Li-Hua, Liu, Hong-Min
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 01.06.2021
Elsevier
Subjects
Chemistry
Chemistry, Medicinal
Chemistry, Organic
Gastric cancer
Histone demethylase
Life Sciences & Biomedicine
LSD1 inhibitor
Pharmacology & Pharmacy
Physical Sciences
Science & Technology
Tranylcypromine
Histone demethylase
LSD1 inhibitor
Tranylcypromine
Gastric cancer
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Summary:[Display omitted] Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.
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ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2021.127993