BB-Cl-amidine trifluoroacetate salt

BB-Cl-amidine is a pan inhibitor of peptidyl arginine deiminases (PADs) and a proteolysis-resistant derivative of Cl-amidine (Item No. 10599).1 It irreversibly inhibits PAD1-4 (kinact/KI = 16,100, 4,100, 6,800, and 13,300 M-1min-1, respectively).2,3 BB-Cl-amidine (20 and 200 µM) inhibits the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate (PMA; Item No. 10008014) without altering hydrogen peroxide (H2O2) production in bone marrow-derived neutrophils.1 It inhibits IFN-β production induced by the DNA virus herpes simplex virus 1 (HSV-1) but not the RNA virus Sendai virus in mouse bone marrow-derived macrophages (BMDMs) when used at a concentration of 1 µM.4 Ex vivo, BB-Cl-amidine (10 mg/kg) reduces BMDM IFN-β and TNF-α production induced by diABZI STING agonist-1 (Item No. 28054) in wild-type, Pad2-/-, and Pad4-/- mice. BB-Cl-amidine (20 mg/kg per day) increases survival, as well as reduces splenomegaly, myocarditis, and cardiac fibrosis in a Trex1D18N/D18N mouse model of Aicardi-Goutières syndrome (AGS).WARNING This product is not for human or veterinary use.

[1] JASON S KNIGHT. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice.[J]. ACS Medicinal Chemistry Letters, 2015: 2199-2206. DOI: 10.1136/annrheumdis-2014-205365
[2] YUAN LUO. Inhibitors and Inactivators of Protein Arginine Deiminase 4: Functional and Structural Characterization†,‡[J]. Biochemistry Biochemistry, 2006, 45 39: 11727-11736. DOI: 10.1021/bi061180d
[3] AARON MUTH. Development of a Selective Inhibitor of Protein Arginine Deiminase 2[J]. Journal of Medicinal Chemistry, 2017, 60 7: 3198-3211. DOI: 10.1021/acs.jmedchem.7b00274
[4] FIACHRA HUMPHRIES. Targeting STING oligomerization with small-molecule inhibitors.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 33: e2305420120. DOI: 10.1073/pnas.2305420120
[5] SELINA PASQUERO . Novel antiviral activity of PAD inhibitors against human beta-coronaviruses HCoV-OC43 and SARS-CoV-2[J]. Antiviral research, 2022, 200: Article 105278. DOI: 10.1016/j.antiviral.2022.105278
[6] YEBIN ZHOU. Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils.[J]. Scientific Reports, 2018: 15228. DOI: 10.1038/s41598-018-33385-z