3LE9

Crystal structure of the catalytic domain of TACE with Indazolinone-phenyl-hydantoin inhibitor

Summary for 3LE9

• Entry DOI: 10.2210/pdb3le9/pdb
• Related: 1BKC 3L0T 3L0V 3LEA
• Descriptor: Disintegrin and metalloproteinase domain-containing protein 17, ZINC ION, (5R)-5-[(5-methoxy-3-oxo-1,3-dihydro-2H-indazol-2-yl)methyl]-5-phenylimidazolidine-2,4-dione, ... (5 entities in total)
• Functional Keywords: glycoprotein, membrane, metal-binding, metalloprotease, notch signaling pathway, phosphoprotein, protease, transmembrane, zymogen, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P78536
• Total number of polymer chains: 2
• Total formula weight: 62033.87

Authors

Orth, P. (deposition date: 2010-01-14, release date: 2010-12-08, Last modification date: 2023-09-06)

Primary citation

Yu, W.,Tong, L.,Kim, S.H.,Wong, M.K.,Chen, L.,Yang, D.Y.,Shankar, B.B.,Lavey, B.J.,Zhou, G.,Kosinski, A.,Rizvi, R.,Li, D.,Feltz, R.J.,Piwinski, J.J.,Rosner, K.E.,Shih, N.Y.,Siddiqui, M.A.,Guo, Z.,Orth, P.,Shah, H.,Sun, J.,Umland, S.,Lundell, D.J.,Niu, X.,Kozlowski, J.A.
Biaryl substituted hydantoin compounds as TACE inhibitors.
Bioorg.Med.Chem.Lett., 20:5286-5289, 2010

PubMed Abstract: We disclose further optimization of hydantoin TNF-alpha convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K(i), good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.

PubMed: 20663669
DOI: 10.1016/j.bmcl.2010.06.134

Experimental method

X-RAY DIFFRACTION (1.85 Å)