Cl-amidine is an orally active inhibitor of peptidyl arginine deminase (PAD) (IC50s: 0.8 μM, 6.2 μM, and 5.9 μM for PAD1, PAD3, and PAD4). Cl-amidine induces apoptosis in cancer cells.

PAD4:5.9 μM

Cl-amidine inhibits all the active PAD isozymes with near equal potency (kinact/KI=13,000/(M?min) 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].

Cl-amidine (75 mg/kg, i.p. once daily) suppresses and treats DSS-induced colitis in mice. Cl-amidine (5, 25, 75 mg/kg, oral gavage, once daily) leads to significant reductions in the histology scores dose-dependently [2].