PAD

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.

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

PAD-PF1 is a PAD4 inhibitor with an IC50 value of 15.9 µM. It binds to an allosteric site on PAD-PF1 that is distinct from the sites where substrates and GSK147 bind to PAD-PF1.

PAD-PF2 is an inhibitor of PAD4, exhibiting a Kd value of 2.82 µM. It effectively suppresses protein citrullination induced by Ionomycin in human neutrophils.

PAD-IN-3 (Compound 16) is a potent dual inhibitor of peptidylarginine deiminase 4 (PAD4) and PAD1, with IC50 values of 0.204 μM and 0.273 μM, respectively. It has potential applications in the research of citrullination-related diseases such as cancer and autoimmune disorders.

PAD-IN-2 is a potent inhibitor of pad4 with an IC50 value <1 μM and can be used to study autoimmune diseases and cancers such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, cutaneous lupus erythematosus, cystic fibrosis, ulcerative colitis, asthma, multiple sclerosis, and psoriasis.

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).

PAD2-IN-1 hydrochloride is a potent and selective protein arginine deiminase 2 (PAD2) inhibitor with superior selectivity for PAD2 over PAD4 (95-fold) and PAD3 (79-fold), and is a benzimidazole-based derivative.

PAD-IN-4 is a potent PAD inhibitor (PAD 1/4, IC50= 0.273/0.24 μM) and exhibits no significant cytotoxicity to A549 or MDA-MB-231 cells. It is useful for research into cancer and autoimmune diseases.

PAD2-IN-2 (cis-isomer of 1) TFA is an inhibitor of protein arginine deiminase 2 (PAD2). This molecule features an azobenzene photoswitch, enabling the optical regulation of PAD activity. Additionally, PAD2-IN-2 TFA inhibits the citrullination of histone H3.

PAD4-IN-4 (compound 28) is a potent PAD4 inhibitor with an IC50 of 0.79±0.09 μM. It reshapes the neutrophil phenotype, increases the proportion of dendritic cells and M1 macrophages, reduces the number of myeloid-derived suppressor cells, and enhances the tumor immune microenvironment. PAD4-IN-4 is applicable for research in triple-negative breast cancer.

PAD2/4-IN-1 is an orally active inhibitor of PAD2 and PAD4, with IC50 values of 23 and 10 nM, respectively. It inhibits protein citrullination in neutrophils and reduces hERG channel toxicity. PAD2/4-IN-1 is applicable in research on autoimmune diseases, neurological disorders, and cancer.

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.

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.

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

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

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

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.

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.

Cl-amidine TFA is an orally active PAD inhibitor with IC₅₀ values of 0.8 μM, 6.2 μM and 5.9 μM for PAD1, PAD3 and PAD4, respectively. This compound can induce cancer cell apoptosis, and also upregulate the expression of miR-16 (miRNA-16, microRNA-16), thereby triggering cell cycle arrest. In addition, Cl-amidine TFA can block the citrullination of histone 3 and the formation of neutrophil extracellular traps, effectively improving the survival rate of mice with sepsis.

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

BB-Cl-Yne is a cell-permeable derivative of the protein arginine deiminase (PAD) inhibitor BB-Cl-amidine that contains an alkyne moiety for use in click chemistry reactions. BB-CL-Yne inhibits PAD1-4 with Kinact/KI values of 6,400, 3,600, 10,800, and 4,900 M-1min-1, respectively. It has been used for labeling PADs in cell-free and cell-based assays, followed by click reactions with azide-modified TAMRA or biotin reporters.

F-amidine is a selective inhibitor of protein arginine deiminases (PADs), specifically targeting PAD1 and PAD4 with in vitro IC50 values of 29.5, 350, and 21.6 µM for PAD1, PAD3, and PAD4, respectively. It irreversibly inactivates all four PAD subtypes by covalently modifying an active site cysteine crucial for enzymatic activity, with kinact/KI values of 2,800, 380, 170, and 3,000 M^-1min^-1. Additionally, F-amidine demonstrates cytotoxicity against HL-60, MCF-7, and HT-29 cancer cell lines, with IC50s of 0.5, 0.5, and 1 μM, respectively.

GSK147 is an inhibitor of PAD4 with a Kd value of 0.469 µM. It effectively suppresses ionomycin-induced protein citrullination in human neutrophils.