Cl-amidine

Cl-amidine 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 induces apoptosis in cancer cells. Cl-amidine induces microRNA (miR)-16 (miRNA-16, microRNA-16) expression and causes cell cycle arrest. Cl-Amidine prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model[1][2][3][4][5].

[1]Yuan Luo, et al. Inhibitors and Inactivators of Protein Arginine Deiminase 4: Functional and Structural Characterization. Biochemistry. 2006 Oct 3; 45(39): 11727–11736.|[2]Chumanevich AA, et al. Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor. Am J Physiol Gastrointest Liver Physiol. 2011 Jun;300(6):G929-38.|[3]Witalison EE, et al. Molecular targeting of protein arginine deiminases to suppress colitis and prevent colon cancer. Oncotarget. 2015 Nov 3;6(34):36053-62.|[4]Biron BM, et al., Cl-Amidine Prevents Histone 3 Citrullination and Neutrophil Extracellular Trap Formation, and Improves Survival in a Murine Sepsis Model. J Innate Immun. 2017;9(1):22-32.|[5]Bryan Knuckley, et al. Substrate Specificity and Kinetic Studies of PADs 1, 3, and 4 Identify Potent and Selective Inhibitors of Protein Arginine Deiminase 3. Biochemistry. 2010 Jun 15;49(23):4852-63.Nat Biomed Eng. 2024 Mar 15.|Neoplasia. 2022 Nov;33:100835.|Research Square Print. January 4th, 2023.|Transl Res. 2022 Nov 23;S1931-5244(22)00252-3.|Vet Parasitol. 2022 Nov 19;312:109841.|Cell Rep. 2021 Sep 21;36(12):109750.|Chem Res Toxicol. 2022 Feb 15.|Fish Shellfish Immunol. 2022 Aug 3;S1050-4648(22)00414-4.|Free Radic Biol Med. 2024 Sep 12:S0891-5849(24)00656-7.|Microb Pathogenesis. 2020 Dec;149:104530.|Microvasc Res. 2023 Aug 9;104592.