Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe

Carolyn N Paulson; Xianghong Guan; Alex M Ayoub; Alice Chan; Rezaul M Karim; William C K Pomerantz; Ernst Schönbrunn; Gunda I Georg; Jon E Hawkinson

doi:10.1021/acsmedchemlett.8b00380

Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe

ACS Med Chem Lett. 2018 Oct 31;9(12):1223-1229. doi: 10.1021/acsmedchemlett.8b00380. eCollection 2018 Dec 13.

Authors

Carolyn N Paulson¹, Xianghong Guan¹, Alex M Ayoub², Alice Chan^{3

4}, Rezaul M Karim^{3

4}, William C K Pomerantz², Ernst Schönbrunn^{3

4}, Gunda I Georg¹, Jon E Hawkinson¹

Affiliations

¹ Department of Medicinal Chemistry and Institute for Therapeutics Discovery & Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, Minneapolis, Minnesota 55414, United States.
² Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, Minnesota 55455, United States.
³ H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, United States.
⁴ Department of Molecular Medicine, University of South Florida, Tampa, Florida 33612, United States.

Abstract

Several chemical probes have been developed for use in fluorescence polarization screening assays to aid in drug discovery for the bromodomain and extra-terminal domain (BET) proteins. However, few of those have been characterized in the literature. We have designed, synthesized, and thoroughly characterized a novel fluorescence polarization pan-BET chemical probe suitable for high-throughput screening, structure-activity relationships, and hit-to-lead potency and selectivity assays to identify and characterize BET bromodomain inhibitors.

Abstract

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