Novel small molecule protein arginine deiminase 4 (PAD4) inhibitors

Murat Bozdag; Tobias Dreker; Christophe Henry; Paolo Tosco; Maura Vallaro; Roberta Fruttero; Andrea Scozzafava; Fabrizio Carta; Claudiu T Supuran

doi:10.1016/j.bmcl.2012.11.102

Novel small molecule protein arginine deiminase 4 (PAD4) inhibitors

Bioorg Med Chem Lett. 2013 Feb 1;23(3):715-9. doi: 10.1016/j.bmcl.2012.11.102. Epub 2012 Dec 2.

Authors

Murat Bozdag¹, Tobias Dreker, Christophe Henry, Paolo Tosco, Maura Vallaro, Roberta Fruttero, Andrea Scozzafava, Fabrizio Carta, Claudiu T Supuran

Affiliation

¹ Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.

PMID: 23265898
DOI: 10.1016/j.bmcl.2012.11.102

Abstract

Protein arginin deaminase 4 (PAD4) is a calcium dependent enzyme which catalyses the conversion of peptidyl-arginine into peptidyl-citrulline and is implicated in several diseases such as rheumatoid arthritis (RA) and cancer. Herein we report the discovery of novel small-molecule, non peptidic PAD4 inhibitors incorporating primary/secondary guanidine moieties.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Guanine / chemistry
Humans
Hydrolases / antagonists & inhibitors*
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Protein-Arginine Deiminase Type 4
Protein-Arginine Deiminases

Substances

Enzyme Inhibitors
Guanine
Hydrolases
PADI4 protein, human
Protein-Arginine Deiminase Type 4
Protein-Arginine Deiminases