6PAF

Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors

6PAF の概要

• エントリーDOI: 10.2210/pdb6paf/pdb
• 関連するPDBエントリー: 6P6G 6P6K 6P7Z
• 分子名称: Histone-lysine N-methyltransferase SMYD3, ZINC ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: methyltransferase, oncology, inhibitor, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50774.46

構造登録者

Elkins, P.A.,Wang, L. (登録日: 2019-06-11, 公開日: 2020-01-15, 最終更新日: 2023-10-11)

主引用文献

Su, D.S.,Qu, J.,Schulz, M.,Blackledge, C.W.,Yu, H.,Zeng, J.,Burgess, J.,Reif, A.,Stern, M.,Nagarajan, R.,Pappalardi, M.B.,Wong, K.,Graves, A.P.,Bonnette, W.,Wang, L.,Elkins, P.,Knapp-Reed, B.,Carson, J.D.,McHugh, C.,Mohammad, H.,Kruger, R.,Luengo, J.,Heerding, D.A.,Creasy, C.L.
Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors.
Acs Med.Chem.Lett., 11:133-140, 2020

PubMed 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 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.

PubMed: 32071679
DOI: 10.1021/acsmedchemlett.9b00493

実験手法

X-RAY DIFFRACTION (1.241 Å)