A Novel Screen of PAD4 Inhibitors


Reference #: 00689

Invention Description:

The subject invention is an Activity-Based Protein Profiling (ABPP) assay in which a potential inhibitor compound competes with rhodamine-conjugated fluoroamidine to bind to PAD4. Fluorescence is measured to determine an estimate of the amount of fluorescent protein arginine deiminase 4 that is present in the assay.

Potenttial Applications:

Protein Arginine Deiminase 4 (PAD4) is a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical.

Advantages and Benefits:

    • Overcomes the limitations of commonly used PAD4 assays by eliminating the need for strong acids, high temperatures, and toxic compounds

    • Allows for the direct visualization of PAD4 inhibition


While additional PAD activity assays have recently been described in the literature (e.g., an ELISA based assay that monitors PAD4 activity through the use of an anti-citrulline antibody28 and a coupled assay that couples the production of ammonia to the glutamate dehydrogenase catalyzed reductive amination of α-ketoglutarate29), these assays provide only an indirect measure of PAD4 activity. In contrast, this assay allows for the direct visualization of PAD4 inhibition.

Furthermore, this invention represents the first use of a competitive ABPP assay to overcome the limitations of previous assays in a system with purified proteins, thereby providing an additional application for ABPP reagents and suggesting a general application for ABPP assays in drug discovery.

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Methods to Identify Protein Arginine Deiminase 4 Inhibitors Utility United States 12/262,436 8,007,996 10/31/2008 8/30/2011 6/17/2029  
For Information, Contact:
Technology Commercialization
University of South Carolina
Paul Thompson
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