pad 2

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.

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

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.

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.

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

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.

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)

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.

Sarpogrelate-d3 HCl is a deuterated compound of Sarpogrelate HCl. Sarpogrelate HCl has a CAS number of 135159-51-2. Sarpogrelate(MCI-9042) hydrochloride, a selective 5-HT2 antagonist, has been widely used as an anti-platelet agent for the treatment of PAD. Target: 5-HT2 Recepter Sarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. Sarpogrelate was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). After 12 weeks of sarpogrelate administration, FBF and LBF responses during RH showed significant increases from 13.2 + - 1.7 to 18.1 + - 2.2 mL min per 100 mL tissue (P < 0.01) and from 8.2 + - 0.9 to 14.2 + - 2.1 mL min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate-induced augmentation of FBF and LBF responses to RH was maintained at 24 weeks. Long-term oral administration of sarpogrelate improves vascular function in patients with PAD.