Protein Arginine Deiminase Inhibitor

GSK484 hydrochloride is a selective and reversible peptidylarginine deiminase 4 (PAD4) inhibitor. GSK484 hydrochloride demonstrates high affinity binding to PAD4 with IC₅₀s of 50 nM in the absence of Calcium. In the presence of 2 mM Calcium, notably lower potency (250 nM) is observed.

Cl-amidine hydrochloride is an orally active peptidylarginine deminase (PAD) inhibitor, with IC₅₀ values of 0.8 μM, 6.2 μM and 5.9 μM for PAD1, PAD3, and PAD4, respectively. Cl-amidine hydrochloride induces apoptosis in cancer cells. Cl-amidine hydrochloride induces microRNA (miR)-16 (miRNA-16, microRNA-16) expression and causes cell cycle arrest. Cl-Amidine hydrochloride prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model.

GSK484 is a PAD4 inhibitor that effectively inhibits protein citrullination and the formation of neutrophil extracellular traps (NETs) by blocking the catalytic activity of PAD4. GSK484 suppresses the production of histone H3, MHC-I expression, CD8⁺ T cell activation, proliferation and inflammatory cytokine release. GSK484 reduces inflammation and bone destruction in collagen-induced rheumatoid arthritis, alleviates pain and mast cell activation in sickle cell disease, and improves myocardial ischemia-reperfusion injury and experimental colitis. In addition, GSK484 restores intestinal microbial homeostasis by reversing ferroptosis-induced dysbiosis. GSK484 can be used to study the disease mechanisms of rheumatoid arthritis, sickle cell disease, thrombosis, myocardial injury, colitis and other conditions.

BB-Cl-Amidine hydrochloride is a peptidylarginine deminase (PAD) inhibitor.

AFM-30a hydrochloride is a potent protein arginine deiminase 2 (PAD2) inhibitor and has excellent PAD2-selectivity. AFM-30a hydrochloride binds to PAD2 with an EC₅₀ value of 9.5 μM. AFM-30a hydrochloride also inhibits H3 citrullination with an EC₅₀ value of 0.4 μM. AFM-30a hydrochloride can be used for the research of certain cancers and a variety of autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis.

Hydroquinine (Dihydroquinine) is an anti-bacterial agent that inhibits both Gram-positive and Gram-negative bacteria. Hydroquinine inhibits the growth of multidrug-resistant pseudomonas aeruginosa via the suppression of the arginine deiminase pathway genes. Hydroquinine inhibits Plasmodium falciparum and Plasmodium berghei. Hydroquinine displays anti-malarial and demelanizing activities. Hydroquinine effectively induces specific RND-type efflux pump systems in Pseudomonas aeruginosa, particularly the MexCD-OprJ and MexXY efflux pumps. Hydroquinine inhibits Pseudomonas aeruginosa adhesion and biofilm formation. Hydroquinine serves as a precursor for derivatives such as C9 epihydroquinine, 9-acetoxy-10,11-dihydroquinine, and 10,11-dihydroquinine monohydrochloride.

CAY10729 (Compound 21) is a selective PAD2 inhibitor. CAY10729 inhibits neutrophil extracellular trap formation.

PADI4_3 is a substrate-competitive and selective PADI4 inhibitor with an IC₅₀ of 56 nM. PADI4_3 blocks citrullination of histone H3 and reduces the formation of neutrophil extracellular traps. PADI4_3 can be used in research related to autoimmune diseases and cancers.

AFM32a (PAD2-IN-1) hydrochloride, a benzimidazole-based derivative, is a potent and selective protein arginine deiminase 2 (PAD2) inhibitor. AFM32a hydrochloride shows superior selectivity for PAD2 over PAD4 (95-fold) and PAD3 (79-fold).

BB-Cl-Amidine is a peptidylarginine deminase (PAD) inhibitor.

GSK199 is an orally active, reversible, and selective PAD4 inhibitor with an IC₅₀ of 200 nM in the absence of calcium. GSK199 can be used for the research of rheumatoid arthritis.

Streptonigrin (Bruneomycin) is an orally active antibiotic and pan-PAD inhibitor, inhibiting PAD1, PAD2, PAD3 and PAD4 with IC₅₀ of 48.3 μM, 26.1 μM, 0.43 μM and 2.5 μM, respectively. Streptonigrin inhibits SENP1 (IC₅₀ of 0.518 μM) and reduces HIF1α. Streptonigrin increases p53 and Apoptosis. Streptonigrin shows antiviral activity against Rauscher murine leukemia virus. Streptonigrin has immunosuppressive effects. Streptonigrin has antitumor activity against osteosarcoma.

JBI-589 is a non-covalent PAD4 isoform-selective inhibitor with oral bioavailability. JBI-589 reduces CXCR2 expression and blocks neutrophil chemotaxis. JBI-589 reduces primary tumor and metastases, and enhances the anti-tumor effect of checkpoint inhibitors. JBI-589 can be used in cancer research.

D-Cl-amidine hydrochloride is a potent and highly selective PAD1 inhibitor. D-Cl-amidine is well-torelated with no significant toxicity.

BMS-P5 is a selective and orally active peptidylarginine deiminase 4 (PAD4) inhibitor with an IC₅₀ of 98 nM. BMS-P5 shows selective for PAD4 over PAD1, PAD2, and PAD3. BMS-P5 blocks multiple myeloma (MM)-induced neutrophil extracellular trap (NET) formation and delays progression of MM in a syngeneic mouse model.

BMS-P5 free base is a selective and orally active peptidylarginine deiminase 4 (PAD4) inhibitor with an IC₅₀ of 98 nM. BMS-P5 free base shows selective for PAD4 over PAD1, PAD2, and PAD3. BMS-P5 free base blocks multiple myeloma (MM)-induced neutrophil extracellular trap (NET) formation and delays progression of MM in a syngeneic mouse model.

GSK121 is a selective PAD4 inhibitor. GSK121 can be used in the research of PAD4-related diseases, including those characterized by abnormal NET levels and various tumors.

GSK106 is an inactive control for the selective PAD4 inhibitors, GSK484 and GSK199.

PAD-IN-2 is a potent pad4 inhibitor (IC₅₀: <1 μM). PAD-IN-2 can be used in the research of auto-immune diseases and cancers, such as rheumatoid arthritis, vasculitis, systemic lupus erythematosis, cutaneous lupus erythematosis, ulcerative colitis, cystic fibrosis, asthma, multiple sclerosis and psoriasis.

PAD4-IN-2 TFA is a highly tumor-targeted and irreversible PAD4 inhibitor with an IC₅₀ of 1.94 μM. PAD4-IN-2 TFA selectively recognizes sialic acid on tumor surfaces and accumulates in tumor tissues, with distribution in the cytoplasm of tumor cells and nuclei of neutrophils. PAD4-IN-2 TFA inhibits the PAD4-H3cit-NETs (Neutrophil Extracellular Traps) pathway, reduces senescent tumor-associated neutrophils, and promotes M1 macrophage polarization. The compound exhibits potent anti-tumor and anti-metastatic activities and is suitable for breast cancer research.