Identification of potent and selective TACE inhibitors via the S1 pocket

Jeffrey S Condon; Diane Joseph-McCarthy; Jeremy I Levin; Henry-Georges Lombart; Frank E Lovering; Linhong Sun; Weiheng Wang; Weixin Xu; Yuhua Zhang

doi:10.1016/j.bmcl.2006.10.004

Identification of potent and selective TACE inhibitors via the S1 pocket

Bioorg Med Chem Lett. 2007 Jan 1;17(1):34-9. doi: 10.1016/j.bmcl.2006.10.004. Epub 2006 Oct 5.

Authors

Jeffrey S Condon¹, Diane Joseph-McCarthy, Jeremy I Levin, Henry-Georges Lombart, Frank E Lovering, Linhong Sun, Weiheng Wang, Weixin Xu, Yuhua Zhang

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.

PMID: 17064892
DOI: 10.1016/j.bmcl.2006.10.004

Abstract

By focusing on the P1 portion of the piperidine beta-sulfone ligands we identified a motif that induces selectivity and resulted in a series of TACE inhibitors that demonstrated excellent in vitro potency against isolated TACE enzyme and excellent selectivity over MMPs 1, 2, 9, 13, and 14.

MeSH terms

ADAM Proteins / antagonists & inhibitors*
ADAM Proteins / chemistry*
ADAM17 Protein
Crystallography, X-Ray
Ligands
Metalloendopeptidases / antagonists & inhibitors
Piperidines / chemistry
Protease Inhibitors / chemistry*
Protease Inhibitors / isolation & purification*
Protease Inhibitors / pharmacology
Sulfones / chemistry

Substances

Ligands
Piperidines
Protease Inhibitors
Sulfones
ADAM Proteins
Metalloendopeptidases
ADAM17 Protein