Discovery of potent, selective human granzyme B inhibitors that inhibit CTL mediated apoptosis

Christopher A Willoughby; Herbert G Bull; Margarita Garcia-Calvo; Joanne Jiang; Kevin T Chapman; Nancy A Thornberry

doi:10.1016/s0960-894x(02)00363-3

Discovery of potent, selective human granzyme B inhibitors that inhibit CTL mediated apoptosis

Bioorg Med Chem Lett. 2002 Aug 19;12(16):2197-200. doi: 10.1016/s0960-894x(02)00363-3.

Authors

Christopher A Willoughby¹, Herbert G Bull, Margarita Garcia-Calvo, Joanne Jiang, Kevin T Chapman, Nancy A Thornberry

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. willoughby@merk.com

PMID: 12127536
DOI: 10.1016/s0960-894x(02)00363-3

Abstract

A novel class of small molecule human granzyme B inhibitors is reported. Compound 20 has a K(i) of 7 nM against human granzyme B and blocks CTL mediated apoptosis with an IC(50) of 3 micromolar.

MeSH terms

Apoptosis / drug effects*
Cytotoxicity, Immunologic / drug effects
Drug Design
Granzymes
Humans
Inhibitory Concentration 50
Molecular Structure
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology*
Structure-Activity Relationship
Substrate Specificity
T-Lymphocytes, Cytotoxic / drug effects*
T-Lymphocytes, Cytotoxic / immunology*

Substances

Serine Proteinase Inhibitors
GZMB protein, human
Granzymes
Serine Endopeptidases