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.

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.

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

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].

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].

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.

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

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.

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

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.

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.

GSK121 is an inhibitor of selective PAD4.

YW3-56 is an inhibitor of protein arginine deiminase 2 (PAD2) and PAD4 (IC50s = 0.5-1 and 1-5 μM, respectively).1It inhibits the growth of U2OS osteosarcoma cells (IC50= ~2.5 μM) in a p53-dependent mannerviainduction of SESN2 and subsequent inhibition of mTORC1. YW3-56 (10 mg kg) reduces tumor growth in an S-180 murine sarcoma tumor model. It also inhibits tumor growth in the 1883 MDA-MB-231 breast cancer bone metastasis mouse xenograft model.2 1.Wang, Y., Li, P., Wang, S., et al.Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activityThe Journal of Biological Chemisty287(31)25941-25952(2012) 2.Wang, S., Chen, X.A., Hu, J., et al.ATF4 gene network mediates cellular response to the anticancer PAD inhibitor YW3-56 in triple-negative breast cancer cellsMol. Cancer Ther.14(4)877-888(2015)

F-amidine is a bioavailable irreversible PAD4 inactivator.

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.

JBI-589 is an isoform-selective, non-covalent inhibitor of PAD4 that diminishes CXCR2 expression and impedes neutrophil chemotaxis. Additionally, it attenuates primary tumor growth and metastases, augmenting the efficacy of checkpoint inhibitors [1].

GSK484 is an effective and reversible inhibitor of peptidyl arginine deaminase 4 (PAD4). GSK484 has a high affinity for binding to PAD4.

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.

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

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