3O64

Crystal structure of catalytic domain of TACE with 2-(2-Aminothiazol-4-yl)pyrrolidine-Based Tartrate Diamides

3O64 の概要

• エントリーDOI: 10.2210/pdb3o64/pdb
• 関連するPDBエントリー: 3KMC 3KME 3LGP
• 関連するBIRD辞書のPRD_ID: PRD_000919
• 分子名称: TACE, ISOPROPYL ALCOHOL, N-{(2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}-3-methyl-L-valyl-N-(2-aminoethyl)-L-alaninamide, ... (7 entities in total)
• 機能のキーワード: hydrolase, adam proteins, enzyme inhibitors, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P78536
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62587.83

構造登録者

Orth, P. (登録日: 2010-07-28, 公開日: 2011-04-20, 最終更新日: 2024-11-06)

主引用文献

Dai, C.,Li, D.,Popovici-Muller, J.,Zhao, L.,Girijavallabhan, V.M.,Rosner, K.E.,Lavey, B.J.,Rizvi, R.,Shankar, B.B.,Wong, M.K.,Guo, Z.,Orth, P.,Strickland, C.O.,Sun, J.,Niu, X.,Chen, S.,Kozlowski, J.A.,Lundell, D.J.,Piwinski, J.J.,Shih, N.Y.,Siddiqui, M.A.
2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors.
Bioorg.Med.Chem.Lett., 21:3172-3176, 2011

PubMed Abstract: TNF-α converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability.

PubMed: 21458257
DOI: 10.1016/j.bmcl.2011.01.002

実験手法

X-RAY DIFFRACTION (1.88 Å)