6DI1

CRYSTAL STRUCTURE OF BTK IN COMPLEX WITH COVALENT FRAGMENT LIGAND

6DI1 の概要

• エントリーDOI: 10.2210/pdb6di1/pdb
• 関連するPDBエントリー: 6di0
• 分子名称: Tyrosine-protein kinase BTK, 4-amino-2-[(3S)-3-(propanoylamino)pyrrolidin-1-yl]pyrimidine-5-carboxamide (3 entities in total)
• 機能のキーワード: lead optimization, fragment screening by x-ray, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31876.60

構造登録者

Jiang, X. (登録日: 2018-05-22, 公開日: 2018-10-17, 最終更新日: 2024-11-20)

主引用文献

Caldwell, R.,Liu-Bujalski, L.,Qiu, H.,Mochalkin, I.,Jones, R.,Neagu, C.,Goutopoulos, A.,Grenningloh, R.,Johnson, T.,Sherer, B.,Gardberg, A.,Follis, A.V.,Morandi, F.,Head, J.
Discovery of a novel series of pyridine and pyrimidine carboxamides as potent and selective covalent inhibitors of Btk.
Bioorg. Med. Chem. Lett., 28:3419-3424, 2018

PubMed Abstract: Btk is an attractive target for the treatment of a range of Bcell malignancies as well as several autoimmune diseases such as murine lupus and rheumatoid arthritis. Several covalent irreversible inhibitors of Btk are currently in development including ibrutinib which was approved for treatment of B-cell malignancies. Herein, we describe our efforts using X-ray guided structure based design (SBD) to identify a novel chemical series of covalent Btk inhibitors. The resulting pyridine carboxamides were potent and selective inhibitors of Btk having excellent enzymatic and cellular inhibitory activity.

PubMed: 30290988
DOI: 10.1016/j.bmcl.2018.09.033

実験手法

X-RAY DIFFRACTION (1.1 Å)