Cl-amidine TFA, an ingestible inhibitor of peptidylarginine deminase (PAD), exhibits IC50 values of 0.8 μM for PAD1, 6.2 μM for PAD3, and 5.9 μM for PAD4. It prompts apoptosis in cancerous cells and stimulates the expression of microRNA-16, leading to cell cycle arrest. Additionally, Cl-amidine TFA blocks the citrullination of histone 3 and the formation of neutrophil extracellular traps, thereby enhancing survival rates in a mouse model of sepsis[1][2][3][4][5]. Cl-amidine, at varying concentrations (0, 5, 10, 15, 20, 25, 50 μg/mL) over a 24-hour period, triggers cell death through apoptosis in TK6 lymphoblastoid cells and HT29 colon cancer cells, with the effect intensifying with higher doses. Notably, HT29 cells exhibit a comparative resistance to the apoptotic effects induced by Cl-amidine[2]. Cl-amidine permanently deactivates PAD enzymes through the covalent alteration of a crucial cysteine residue within the active site, which is essential for the enzyme's catalytic function[4].
Cl-amidine TFA 动物研究
Animal study
Cl-amidine, administered intraperitoneally at a dose of 75 mg/kg daily, alleviates and manages colitis in mice induced by DSS. When given orally at doses of 5, 25, and 75 mg/kg once a day, Cl-amidine consistently and dose-dependently decreases histological scores. Specifically, a dosage of 75 mg/kg given intraperitoneally each day results in the suppression of PAD activity, protein citrullination, and PAD levels within the colon in vivo[2].
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