[Description]:
Cl-amidine TFA 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 TFA induces apoptosis in cancer cells. Cl-amidine TFA induces microRNA (miR)-16 expression and causes cell cycle arrest. Cl-Amidine TFA prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model[1][2][3][4][5].
[Related Catalog]:
[Target]
IC50: 0.8 μM (PAD1), 5.9 μM (PAD4), 6.2 μM (PAD3)[1][5].
[In Vitro]
Cl-amidine is a bioavailable haloacetamidine-based compound that inhibits all the active PAD isozymes with near equal potency (kinact/KI=13,000 M-1•min-1 for PAD4)[1]. Cl-amidine (0, 5, 10, 15, 20, 25, 50 μg/mL, 24 hours) induces apoptosis in TK6 lymphoblastoid cells and HT29 colon cancer cells in a dose-dependent manner. Interestingly, the colon cancer cell line (HT29) is relatively resistant to apoptosis caused by Cl-amidine[2]. Cl-amidine irreversibly inactivates PADs by covalently modifying an active site cysteine that is important for its catalytic activity[4]. Apoptosis Analysis[2]. Cell Line: TK6 lymphoblastoid cells and HT29 colon cancer cells. Concentration: 0, 5, 10, 15, 20, 25, 50 μg/mL. Incubation Time: 24 h. Result: Induced apoptosis dose-dependently.
[In Vivo]
Cl-amidine (75 mg/kg, ip once daily) suppresses and treats DSS-induced colitis in mice[2]. Cl-amidine (5, 25, 75 mg/kg, oral gavage, once daily) leads to significant reductions in the histology scores dose-dependently[2]. Animal Model: C57BL/6 mice (8-12 wk old, DSS mouse model of colitis)[2]. Dosage: 75 mg/kg. Administration: IP once daily. Result: Suppressed PAD activity, protein citrullination, and PAD levels in the colon in vivo. Animal Model: C57BL/6 mice (8-12 wk old, DSS mouse model of colitis)[2]. Dosage: 5, 25, 75 mg/kg. Administration: Oral gavage once daily. Result: Led to significant reductions in the histology scores.
[References]