3F7H

Structure of an ML-IAP/XIAP chimera bound to a peptidomimetic

3F7H の概要

• エントリーDOI: 10.2210/pdb3f7h/pdb
• 関連するPDBエントリー: 1tw6 2i3h 2i3i 3F7G 3F7I
• 分子名称: Baculoviral IAP repeat-containing protein 7, ZINC ION, N-[(3aR,6S,6aS)-1-(N-methyl-L-alanyl-3-methyl-L-valyl)octahydrocyclopenta[b]pyrrol-6-yl]-2,2-diphenylacetamide, ... (7 entities in total)
• 機能のキーワード: zinc binding, peptide complex, apoptosis inhibition, peptidomimetic, small molecule, drug design, apoptosis, metal-binding, nucleus, zinc-finger
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31463.65

構造登録者

Franklin, M.C.,Fairbrother, W.J.,Cohen, F. (登録日: 2008-11-09, 公開日: 2009-03-17, 最終更新日: 2024-04-03)

主引用文献

Cohen, F.,Alicke, B.,Elliott, L.O.,Flygare, J.A.,Goncharov, T.,Keteltas, S.F.,Franklin, M.C.,Frankovitz, S.,Stephan, J.P.,Tsui, V.,Vucic, D.,Wong, H.,Fairbrother, W.J.
Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold
J.Med.Chem., 52:1723-1730, 2009

PubMed Abstract: A series of IAP antagonists based on an azabicyclooctane scaffold was designed and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values of 140, 38, and 33 nM, respectively. These compounds promote degradation of c-IAP1, activate caspases, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Finally, compound 14b inhibits tumor growth when dosed orally in a breast cancer xenograft model.

PubMed: 19228017
DOI: 10.1021/jm801450c

実験手法

X-RAY DIFFRACTION (1.8 Å)