Although a lot of efforts have been made to develop specific and potent STAT3 inhibitors, the reported inhibitors still suffer from multiple challenges, such as low specificity, weak binding affinity, low oral bioavailability, poor solubility, structural instability, unfavorable PK profiles, potential severe toxicities, and notably, none of STAT3 inhibitors has been approved for lung cancer therapy in clinic 43. The gene discussed is STAT3; the disease is lung carcinoma.