3B92

Novel thio-based TACE inhibitors Part 2: Rational design, synthesis and SAR of thiol-contaning aryl sufones

Summary for 3B92

• Entry DOI: 10.2210/pdb3b92/pdb
• Descriptor: ADAM 17, ZINC ION, 3-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiol, ... (4 entities in total)
• Functional Keywords: tnf-alpha converting enzyme, aryl-sulfonamide, tace inhibitors, alternative splicing, cleavage on pair of basic residues, glycoprotein, hydrolase, membrane, metal-binding, metalloprotease, notch signaling pathway, phosphorylation, protease, sh3-binding, transmembrane, zinc, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P78536
• Total number of polymer chains: 1
• Total formula weight: 29652.95

Authors

Wei, Y. (deposition date: 2007-11-02, release date: 2007-12-18, Last modification date: 2024-10-16)

Primary citation

Bandarage, U.K.,Wang, T.,Come, J.H.,Perola, E.,Wei, Y.,Rao, B.G.
Novel thiol-based TACE inhibitors. Part 2: Rational design, synthesis, and SAR of thiol-containing aryl sulfones.
Bioorg.Med.Chem.Lett., 18:44-48, 2008

PubMed Abstract: A series of potent thiol-containing aryl sulfone TACE inhibitors were designed and synthesized. The SAR and MMP selectivity of the series were investigated. In particular, compound 8b showed excellent in vitro potency against the isolated enzyme and good selectivity over MMP-2, -7, -8, -9, and -13. The X-ray structure of 8b in complex with TACE was also obtained.

PubMed: 18054488
DOI: 10.1016/j.bmcl.2007.11.014

Experimental method

X-RAY DIFFRACTION (2 Å)