GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2)

• Published in: ACS medicinal chemistry letters Vol. 8; no. 7; pp. 737 - 741
• Main Authors: Crawford, Terry D, Audia, James E, Bellon, Steve, Burdick, Daniel J, Bommi-Reddy, Archana, Côté, Alexandre, Cummings, Richard T, Duplessis, Martin, Flynn, E. Megan, Hewitt, Michael, Huang, Hon-Ren, Jayaram, Hariharan, Jiang, Ying, Joshi, Shivangi, Kiefer, James R, Murray, Jeremy, Nasveschuk, Christopher G, Neiss, Arianne, Pardo, Eneida, Romero, F. Anthony, Sandy, Peter, Tang, Yong, Taylor, Alexander M, Tsui, Vickie, Wang, Jian, Wang, Shumei, Wang, Yongyun, Xu, Zhaowu, Zawadzke, Laura, Zhu, Xiaoqin, Albrecht, Brian K, Magnuson, Steven R, Cochran, Andrea G
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.07.2017; Amer Chemical Soc; American Chemical Society (ACS)
• Subjects: 60 APPLIED LIFE SCIENCES; bromodomain; CECR2; Chemistry, Medicinal; Epigenetics; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; probe; Science & Technology; Epigenetics; CECR2; Bromodomain; Probe; COMPLEX; PROTEIN; RECOGNITION; CBP/EP300; ACETYLATION; HISTONE; FORMS; PROGRESS; NEURULATION
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/acsmedchemlett.7b00132

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.