The role of chlorine atom on the binding between 2-phenyl-1H-benzimidazole analogues and fat mass and obesity-associated protein

In this work, nine 2-phenyl-1H-benzimidazole structural analogues were screened for potential inhibitor of the fat mass and obesity-associated protein (FTO) by isothermal titration calorimetry (ITC). The results show that the binding between 6-chloro-2-phenyl-1H-benzimidazole (1d) and FTO was dominated by entropy. Results of enzymatic activity assays provided an IC50 value of 24.65 mu M for 1d. Our previous results and comparison of nine structural analogues indicated that the chlorine atom was crucial for the binding of small molecules with FTO. The identification of novel small molecules may provide information for the design of FTO inhibitors and the treatment of leukemia.