Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors
Year: 2019
Type: article
Abstract: We report herein the discovery of isoxazole amides as potent and selective SET and MYND Domain-Containing Protein 3 (SMYD3) inhibitors. Elucidation of the structure–activity relationship of the high-throughput screening (HTS) lead compound 1 provided potent and selective SMYD3 inhibitors. The SAR optimization, cocrystal structures of small molecules with SMYD3, and mode of inhibition (MOI) characterization of compounds are described. The synthesis and biological and pharmacokinetic profiles of compounds are also presented.
Source: ACS Medicinal Chemistry Letters
Authors: Dai-Shi Su, Junya Qu, Mark Schulz, Chuck W. Blackledge, Hongyi Yu, Jenny Zeng, Joelle Burgess, Alexander Reif, Melissa Stern, Raman Nagarajan, Melissa Baker Pappalardi, Kristen Wong, Alan P. Graves, William Bonnette, Liping Wang, Patricia Elkins, Beth Knapp-Reed, Jeffrey D. Carson, Charles McHugh, Helai Mohammad, Ryan Kruger, Juan Luengo, Dirk A. Heerding, Caretha L. Creasy
Institution: GlaxoSmithKline (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2998342912