pad4

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.

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

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

GSK121 is an inhibitor of selective PAD4.

Bongkrekic acid (ammonium salt) is a natural product, a mitochondrial adenine nucleotide translocase (ANT) inhibitor that induces neutrophil extracellular trap formation through signaling pathways such as p38 and ERK, and is used for research on mitochondrial function and immune response.

Anti-PAD4 Antibody is an antibody targeting PAD4. It can be used for tumor microenvironment, fibrosis, and inflammation research.

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).

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.

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.

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.

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.

3-(4-Hydroxyphenyl) propionic acid-D4 is a deuterated compound of 3- (4-Hydroxyphenyl)propionic acid (T2862). 3- (4-Hydroxyphenyl)propionic acid has a CAS number of 501-97-3. Desaminotyrosine is a microbially associated metabolite protecting from influenza through augmentation of type I interferon signaling.

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.

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

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.

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.

F-amidine is a bioavailable irreversible PAD4 inactivator.

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

YW3-56 is a potent peptidylarginine deiminase (PAD) inhibitor, with an IC50 of 1-5 μM for PAD4. Compared with Cl-amidine, YW3-56 shows >60-fold increase in cell growth inhibition efficacy (IC50 about 2.5 μM) but only 5-fold increase in PAD4 inhibition (IC sub>50 about 1-5 μM). At 2-4 μM concentrations, YW3-56 displays mainly cytostatic effects by slowing cell division, whereas at higher concentrations, it exerts cytotoxic effects by altering cell morphology and killing cells[1]. [1]. Wang Y, et al. Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and t he mammalian target of rapamycin complex 1 activity. J Biol Chem. 2012 Jul 27;287(31):25941-53.