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Identification of potent and selective TACE inhibitors via the S1 pocket
Jeffrey S Condon1, Diane Joseph-McCarthy, Jeremy I Levin
1Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
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.
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