Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.

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Knuckley B, Luo Y, Thompson PR

Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.

Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Epub 2007 Oct 13.

PubMed ID

17964793 [ View in PubMed

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Abstract

Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Azithromycin	Protein-arginine deiminase type-4	Protein	Humans	Unknown	Inhibitor	Details
Chlortetracycline	Protein-arginine deiminase type-4	Protein	Humans	Unknown	Inhibitor	Details
Streptomycin	Protein-arginine deiminase type-4	Protein	Humans	No	Inhibitor	Details
Tetracycline	Protein-arginine deiminase type-4	Protein	Humans	Unknown	Not Available	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Azithromycin	Protein-arginine deiminase type-4	IC 50 (nM)	>10000000	N/A	N/A	Details
Tetracycline	Protein-arginine deiminase type-4	IC 50 (nM)	780000	N/A	N/A	Details