Design and Synthesis of Styrenylcyclopropylamine LSD1 Inhibitors

Leveraging the catalytic machinery of LSD1 (KDM1A), a series of covalent styrenylcyclopropane LSD1 inhibitors were identified. These inhibitors represent a new class of mechanism-based inhibitors that target and covalently label the FAD cofactor of LSD1. The series was rapidly progressed to potent b...

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Veröffentlicht in:	ACS medicinal chemistry letters 2020-06, Vol.11 (6), p.1213-1220
Hauptverfasser:	Gehling, Victor S, McGrath, John P, Duplessis, Martin, Khanna, Avinash, Brucelle, Francois, Vaswani, Rishi G, Côté, Alexandre, Stuckey, Jacob, Watson, Venita, Cummings, Richard T, Balasubramanian, Srividya, Iyer, Priyadarshini, Sawant, Priyanka, Good, Andrew C, Albrecht, Brian K, Harmange, Jean-Christophe, Audia, James E, Bellon, Steven F, Trojer, Patrick, Levell, Julian R
Format:	Artikel
Sprache:	eng
Schlagworte:	Letter
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Zusammenfassung:	Leveraging the catalytic machinery of LSD1 (KDM1A), a series of covalent styrenylcyclopropane LSD1 inhibitors were identified. These inhibitors represent a new class of mechanism-based inhibitors that target and covalently label the FAD cofactor of LSD1. The series was rapidly progressed to potent biochemical and cellular LSD1 inhibitors with good physical properties. This effort resulted in the identification of , a highly potent (
ISSN:	1948-5875 1948-5875
DOI:	10.1021/acsmedchemlett.0c00060