PAD

GSK484 hydrochloride (GTPL8577) is a reversible peptidyl-arginine deiminase 4 (PAD4) inhibitor. It binds to PAD4 with high affinity, with IC50 of 250 and 50 nM in the presence and absence of 2 mM calcium, respectively. GSK484 promotes the radiosensitivity of colorectal cancer (CRC) and inhibits NET formation in vitro and in vivo.

Cl-amidine hydrochloride is an orally available PAD inhibitor that blocks histone 3 deimination and neutrophil extracellular trap formation and improves survival in septic mice. It induces apoptosis in cancer cells and induces miR-16 to cause cell cycle arrest.

BMS-P5 is a specific and orally active Peptidylarginine Deiminase 4 (PAD4) inhibitor.

GSK121 is an inhibitor of selective PAD4.

BMS-P5 free base is a specific and orally active peptidylarginine deiminase 4 (PAD4) inhibitor that blocks the formation of Neutrophil Extracellular Traps and delays the progression of multiple myeloma. Administration of BMS-P5 to multiple myeloma-bearing mice delays symptom onset and disease progression. Targeting PAD4 may be beneficial for treating multiple myeloma.

GSK199 is a selective PAD4 inhibitor(IC50 of 200 nM in the absence of calcium).

BB-Cl-Amidine is an inhibitor of peptidyl arginine deminase (PAD).

KP-302 (compound 23) is a selective protein arginine deaminase 2 (PAD2) inhibitor with a Ki of 60 μM, capable of reversing physical disability in multiple sclerosis (MS) mice and clearing T-cell infiltration in the brain.

Acefylline (Theophylline-7-acetic acid), a stimulant drug of the xanthine chemical class, acts as an adenosine receptor antagonist. It is combined with diphenhydramine in the pharmaceutical preparation Etanautine to help offset its stimulant effects

N-[1-(Aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]benzamide is a racemic form of Cl-amidine (S enantiomer). Cl-amidine is an orally active peptidylarginine deminase (PAD) inhibitor.

Bongkrekic acid (Bongkrekic Acid (ammonium salt)) is a mitochondrial toxin secreted by Burkholderia gladioli that inhibits adenine nucleotide translocase (ANT).Bongkrekic acid Bongkrekic acid Bongkrekic acid induces extracellular traps in neutrophils through signaling mediated by p38, ERK, PAD4, and P2X1.

D-Cl-amidine is an effective and highly selective PAD1 inhibitor. D-Cl-amidine has a good correlation and no obvious toxicity.

Cl-amidine is an orally active inhibitor of peptidyl arginine deiminase (PAD) with IC50 values of 0.8 μM, 6.2 μM, and 5.9 μM for PAD1, PAD3, and PAD4, respectively. It induces apoptosis in cancer cells.

PAD-IN-2, a potent inhibitor of PAD4 with an IC50 value <1 μM, can be utilized to study autoimmune diseases and cancers, including rheumatoid arthritis, vasculitis, systemic lupus erythematosus, cutaneous lupus erythematosus, cystic fibrosis, ulcerative colitis, asthma, multiple sclerosis, and psoriasis.

PAD2-IN-1, a benzimidazole-based derivative, is an efficacious and specific inhibitor of protein arginine deiminase 2 (PAD2). Demonstrating remarkable selectivity, PAD2-IN-1 exhibits a 95-fold higher affinity for PAD2 in comparison to PAD4 and a 79-fold higher affinity than PAD3.

PAD4-IN-5 (Example 18) is a PAD4 inhibitor with an IC50 of ≤10 nM at 50 µM Ca2+ and 101-500 nM at 1 mM Ca2+ against human PAD4 (hPAD4). This compound is applicable in the study of autoimmune diseases such as rheumatoid arthritis (RA).

Streptonigrin is a natural product produced by Streptomyces flocculus, has both anti-tumor and anti-bacterial activity. Streptonigrin acts as a pan-PAD inhibitor (IC50s: 48.3±34.2 µM, 26.1±0.3 µM, 0.43±0.03 µM, and 2.5±0.4 µM for PAD1, PAD2, PAD3, and PAD

CAY10723 is an inhibitor of protein arginine deiminase 2 (PAD2) that binds to PAD2 in a target engagement assay (EC50 = 9.5 μM in HEK293/PAD2 cells). It is 1.6-, 47-, and ~15-fold selective for PAD2 over PAD1, PAD3, and PAD4, respectively. CAY10723 inhibits histone H3 citrullination in HEK293/PAD2 cells (EC50 = 0.4 μM).

PAD4-IN-2 (compound 5i) is a PAD4 inhibitor with an IC50 of 1.94 μM, demonstrated to suppress tumor growth in mice by specifically inhibiting the PAD4-H3cit-NETs pathway in neutrophils [1].

BB-Cl-Amidine hydrochloride is an inhibitor of peptidylarginine deminase (PAD) [1].

AFM-30a hydrochloride is a potent and highly selective inhibitor of protein arginine deiminase 2 (PAD2). AFM-30a hydrochloride binds to PAD2 (EC50: 9.5 μM) and inhibits H3 guanylation (EC50: 0.4 μM). AFM-30a hydrochloride can be used to study certain cancers and autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis.

GSK106 is a negative control used in binding and functional assays for PAD4 inhibitors.

Acefylline piperazine is a stimulant drug of the xanthine chemical class. It acts as an adenosine receptor antagonist. Acephylline piperazine is a theophylline derivative with a direct bronchodilator action. It has the advantages over theophylline in being far less toxic and producing minimal gastric irritation. It is indicated for the treatment of asthma, emphysema, acute and chronic bronchitis associated with bronchospasm.Acefylline relaxes smooth muscles, relieves bronchospasm & has a stimulant effect on respiration. It stimulates the myocardium & central nervous system, decreases peripheral resistance & venous pressure & causes diuresis. The mechanism of action is still not clear, inhibition of phosphodiesterase with a resulting increase in intracellular cyclic AMP does occur, but not apparently at concentrations normally used for clinical effect. Other proposed mechanisms of action include adenosine receptor antagonism, prostaglandin antagonism & effects on intracellular......

PAD4-IN-3 (compound 4B), a PAD4 inhibitor, exhibits antitumor properties both in vitro and in vivo. It is covalently attached to a peptide-modified chitosan (K-CRGDV), creating an enhanced oxidative stress-responsive nanoagent. This compound, designated as K-CRGDV-PAD4-IN-3, targets tumors actively, inhibits PAD4 activity, prevents the formation of neutrophil extracellular traps (NETs), and enhances the tumor immune microenvironment [1].