2A8H

Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor

Summary for 2A8H

• Entry DOI: 10.2210/pdb2a8h/pdb
• Related: 1ZXC 1bkc
• Descriptor: ADAM 17, ZINC ION, 4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE, ... (4 entities in total)
• Functional Keywords: tace/adam-17, tace-inhibitor complex, zn-endopeptidase, 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: 62378.53

Authors

Levin, J.I.,Chen, J.M.,Laakso, L.M.,Du, M.,Schmid, J.,Xu, W.,Cummons, T.,Xu, J.,Jin, G.,Barone, D.,Skotnicki, J.S. (deposition date: 2005-07-08, release date: 2006-02-07, Last modification date: 2024-10-30)

Primary citation

Levin, J.I.,Chen, J.M.,Laakso, L.M.,Du, M.,Schmid, J.,Xu, W.,Cummons, T.,Xu, J.,Jin, G.,Barone, D.,Skotnicki, J.S.
Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.
Bioorg.Med.Chem.Lett., 16:1605-1609, 2006

PubMed Abstract: A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.

PubMed: 16426848
DOI: 10.1016/j.bmcl.2005.12.020

Experimental method

X-RAY DIFFRACTION (2.3 Å)