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

Article Details

Citation

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
]
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
DrugTargetKindOrganismPharmacological ActionActions
AzithromycinProtein-arginine deiminase type-4ProteinHumans
Unknown
Inhibitor
Details
StreptomycinProtein-arginine deiminase type-4ProteinHumans
No
Inhibitor
Details
TetracyclineProtein-arginine deiminase type-4ProteinHumans
Unknown
Not AvailableDetails
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AzithromycinProtein-arginine deiminase type-4IC 50 (nM)>10000000N/AN/ADetails
TetracyclineProtein-arginine deiminase type-4IC 50 (nM)780000N/AN/ADetails