7AYH

Crystal structure of Aurora A in complex with 7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-one derivative (compound 2c)

7AYH の概要

• エントリーDOI: 10.2210/pdb7ayh/pdb
• 分子名称: Aurora kinase A, 7-[2-[(4-methoxyphenyl)amino]pyrimidin-4-yl]-1,3,4,5-tetrahydro-1-benzazepin-2-one (2 entities in total)
• 機能のキーワード: kinase, kinase inhibitor, aurora kinase, stk6, structural genomics, structural genomics consortium, sgc, transferase
• 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: 33309.19

構造登録者

Chaikuad, A.,Karatas, M.,Kunick, C.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2020-11-12, 公開日: 2021-01-13, 最終更新日: 2024-01-31)

主引用文献

Karatas, M.,Chaikuad, A.,Berger, B.,Kubbutat, M.H.G.,Totzke, F.,Knapp, S.,Kunick, C.
7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-ones Designed by a "Cut and Glue" Strategy Are Dual Aurora A/VEGF-R Kinase Inhibitors.
Molecules, 26:-, 2021

PubMed Abstract: Although overexpression and hyperactivity of protein kinases are causative for a wide range of human cancers, protein kinase inhibitors currently approved as cancer drugs address only a limited number of these enzymes. To identify new chemotypes addressing alternative protein kinases, the basic structure of a known PLK1/VEGF-R2 inhibitor class was formally dissected and reassembled. The resulting 7-(2-anilinopyrimidin-4-yl)-1-benzazepin-2-ones were synthesized and proved to be dual inhibitors of Aurora A kinase and VEGF receptor kinases. Crystal structures of two representatives of the new chemotype in complex with Aurora A showed the ligand orientation in the ATP binding pocket and provided the basis for rational structural modifications. Congeners with attached sulfamide substituents retained Aurora A inhibitory activity. In vitro screening of two members of the new kinase inhibitor family against the cancer cell line panel of the National Cancer Institute (NCI) showed antiproliferative activity in the single-digit micromolar concentration range in the majority of the cell lines.

PubMed: 33799460
DOI: 10.3390/molecules26061611

実験手法

X-RAY DIFFRACTION (2.8 Å)