3B28

Hsp90 alpha N-terminal domain in complex with an inhibitor CH5015765

3B28 の概要

• エントリーDOI: 10.2210/pdb3b28/pdb
• 関連するPDBエントリー: 3B24 3B25 3B26 3B27
• 分子名称: Heat shock protein HSP 90-alpha, GLYCEROL, 4-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-(methylsulfanyl)-1,3,5-triazin-2-amine, ... (5 entities in total)
• 機能のキーワード: chaperone-chaperone inhibitor complex, chaperone/chaperone inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07900
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52406.27

構造登録者

Fukami, T.A.,Ono, N. (登録日: 2011-07-21, 公開日: 2011-09-14, 最終更新日: 2024-03-13)

主引用文献

Miura, T.,Fukami, T.A.,Hasegawa, K.,Ono, N.,Suda, A.,Shindo, H.,Yoon, D.O.,Kim, S.J.,Na, Y.J.,Aoki, Y.,Shimma, N.,Tsukuda, T.,Shiratori, Y.
Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design
Bioorg.Med.Chem.Lett., 21:5778-5783, 2011

PubMed Abstract: Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models.

PubMed: 21875802
DOI: 10.1016/j.bmcl.2011.08.001

実験手法

X-RAY DIFFRACTION (1.35 Å)