8TIC

Structure of human beta 1,3-N-acetylglucosaminyltransferase 2 with compound 1

8TIC の概要

• エントリーDOI: 10.2210/pdb8tic/pdb
• 関連するPDBエントリー: 8SZ3
• 分子名称: N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: acetylglucosaminyltransferase, inhibitor, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 189805.59

構造登録者

Sudom, A.,Min, X. (登録日: 2023-07-19, 公開日: 2023-12-06, 最終更新日: 2024-11-13)

主引用文献

Jackson, J.J.,Siegmund, A.C.,Bai, W.J.,Reed, A.B.,Birkholz, A.B.,Campuzano, I.D.G.,Crequer-Grandhomme, A.,Hu, R.,Modak, R.V.,Sudom, A.,Javier, N.,Sanders, C.,Lo, M.C.,Xie, F.,Cee, V.J.,Manzanillo, P.,Allen, J.G.
Imidazolone as an Amide Bioisostere in the Development of beta-1,3- N -Acetylglucosaminyltransferase 2 (B3GNT2) Inhibitors.
J.Med.Chem., 66:16120-16140, 2023

PubMed Abstract: B3GNT2 is responsible for elongation of cell surface long-chain polylactosamine, which influences the regulation of the immune response, making it an attractive target for immunomodulation. In the development of amide containing B3GNT2 inhibitors guided by structure-based drug design, imidazolones were found to successfully serve as amide bioisosteres. This novel imidazolone isosteric strategy alleviated torsional strain of the amide bond on binding to B3GNT2 and improved potency, isoform selectivity, as well as certain physicochemical and pharmacokinetic properties. Herein, we present the synthesis, SAR, X-ray cocrystal structures, and PK properties of imidazol-4-ones in the context of B3GNT2 inhibition.

PubMed: 37988652
DOI: 10.1021/acs.jmedchem.3c01517

実験手法

X-RAY DIFFRACTION (2.7 Å)