AC-73 is an orally available Cluster of Differentiation 147 (CD147) inhibitor with high bioavailability that selectively disrupts the dimerization of CD147 (the binding site is in the N-terminal IgC2 domain of CD147 including Glu64 and Glu73), resulting in inhibition of the CD147/ERK1/2/STAT3/MMP-2 pathway and inhibition of liver cancer cell motility and invasion. AC-73 has antiproliferative activity and induces autophagy in leukemia cells.

AC-73 (5-10 μM; 24 hours; SMMC-7721 and Huh-7 cells) treatment results in a dose-dependent reduction in the migration and invasion of these HCC cell lines, with no significant effect on cell viability at 20 μM. AC-73 potentially binds to CD147 at Glu64 and Glu73 in the N-terminal IgC2 domain, which are located within the CD147 dimer interface. AC-73 (5-10 μM; 24 hours; SMMC-7721 cells), at 10 μM, significantly inhibits the mRNA expression of MMP-2 and MMP-9, especially MMP-2, without affecting MMP-1, MMP-3, MMP-7, MMP-11, or MMP-13, and reduces MMP-2 mRNA levels and protein secretion as confirmed by RT-qPCR and gelatin zymography. AC-73 (5-20 μM; 6 hours; SMMC-7721 cells) also dose-dependently attenuates ERK1/2 and STAT3 phosphorylation.

AC-73 (25-50 mg/kg; Injected; daily; for 3 weeks; Male BALB/c nu/nu mice with SMMC-7721 cells) treatment significantly decreases the incidence of metastatic foci in nude mice, inhibits the phosphorylation of ERK1/2 and STAT3 in a dose-dependent manner, and reduces MMP-2, but does not inhibit tumor cell proliferation in vivo.[1]