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]}. IC50 & 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 (k_inact/K_I=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]. 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].