The invention discloses an MIF small-molecule inhibitor as well as a
screening method and application thereof, and belongs to the technical field of
medicinal chemistry. The inhibitor is composed of seven compounds with specific structures and pharmaceutically acceptable salts thereof, and the compounds and the pharmaceutically acceptable salts can effectively inhibit the tautomerase activity of MIF. The lead compounds are efficiently found from a large number of compounds through a computer-aided
virtual screening method. In-vitro and in-vivo experiments show that the compound F3277-0933, especially the compound F3277-0933, shows remarkable MIF inhibitory activity and anti-tumor effect in
enzyme level,
cellular level and animal models, and the effect of the compound F3277-0933 is superior to that of an existing inhibitor ISO-1. The MIF small-molecule inhibitor disclosed by the invention provides a new candidate compound for developing medicines for treating MIF-related diseases such as
colorectal cancer.