Inhibitors/inactivators of protein arginine deiminase 4

ORGN 637

Paul R. Thompson, thompson@mail.chem.sc.edu, Department of Chemistry & Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, SC 29208
A group of small molecule inhibitors and inactivators of PAD4 have been successfully synthesized and tested. Some of these small molecules are reversible competitive inhibitors of PAD4; whereas others are irreversible inactivators of PAD4 with IC50 values in the low micromolar range. These molecules are the most potent PAD4 inhibitors and/or inactivators that have ever been reported. Optimization based on these molecules will give rise to more potent and selective PAD4 inhibitors/inactivators that can ultimately be used as treatments for Rheumatoid Arthritis and Multiple Sclerosis.