6GI6

Crystal structure of the ACVR1 (ALK2) kinase in complex with a Quinazolinone based ALK2 inhibitor with a 5-methyl core.

6GI6 の概要

• エントリーDOI: 10.2210/pdb6gi6/pdb
• 分子名称: Activin receptor type-1, 5-methyl-6-quinolin-5-yl-3~{H}-quinazolin-4-one, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: kinase, bmp, inhibitor, signalling, signaling protein
• 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: 35829.88

構造登録者

Williams, E.,Hudson, L.,Bezerra, G.A.,Sorrell, F.,Mahajan, P.,Kupinska, K.,Hoelder, S.,Burgess-Brown, N.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bullock, A.N. (登録日: 2018-05-10, 公開日: 2018-05-23, 最終更新日: 2024-01-17)

主引用文献

Hudson, L.,Mui, J.,Vazquez, S.,Carvalho, D.M.,Williams, E.,Jones, C.,Bullock, A.N.,Hoelder, S.
Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept.
J. Med. Chem., 61:7261-7272, 2018

PubMed Abstract: Structure-activity relationship and crystallographic data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes to discover potent inhibitors and characterized the chemical modifications that triggered the flip in binding mode. We report kinase selectivity and demonstrate that compounds of this series modulate ALK2 in cancer cells. These inhibitors are attractive starting points for the discovery of more advanced ALK2 inhibitors.

PubMed: 30085668
DOI: 10.1021/acs.jmedchem.8b00782

実験手法

X-RAY DIFFRACTION (1.98 Å)