AC-73是ClusterofDifferentiation147(CD147)的第一种特定的口服生物利用的抑制剂，可特异性破坏CD147的二聚化(结合位点在CD147的N端IgC2域中包括Glu64和Glu73)，从而抑制CD147/ERK1/2/STAT3/MMP-2途径，并抑制肝癌细胞的运动和侵袭。AC-73还是一种抗增殖药，也是白血病细胞自噬的诱导剂。
AC-73 is a first specific, orally active inhibitor of cluster of differentiation 147 (CD147), which specifically disrupts CD147 dimerization, thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways. AC-73 inhibits the motility and invasion of hepatocellular carcinoma cells[1]. AC-73 is also an anti-proliferative drug and an inducer of autophagy in leukemic cells[2].
AC-73 (5-10 μM; 24 hours; SMMC-7721 and Huh-7 cells) treatment significantly decreases the migration ability of SMMC-7721 and Huh-7 cells in a dose-dependent manner and decreases the invasion of two HCC cells in a dose-dependent manner at 24 hours. AC-73 treatment reduces HCC metastases. There are no obvious effects on cell viability when two HCC cells are treated with AC-73 at a maximum concentration of 20 μM. The possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147[1]. AC-73 (5-10 μM; 24 hours; SMMC-7721 cells) treatment could significantly inhibit both MMP-2 and MMP-9 mRNA expression at the concentration of 10 μM, especially MMP-2, but no obvious effect on MMP-1, MMP-3, MMP-7, MMP-11 nor MMP-13. AC-73 could dose dependently reduce the expression of MMP-2 mRNA level and secretion of the protein level using RT-qPCR analysis and gelatin zymography experiments[1].AC-73 (5-20 μM; 6 hours; SMMC-7721 cells) treatment dose-dependently suppresses the phosphorylation of ERK1/2 and STAT3[1]. RT-PCR[1] Cell Line: SMMC-7721 cells
AC-73 (25-50 mg/kg; for 4 weeks; Male BALB/c nu/nu mice) treatment significantly decreases the incidence of metastatic foci in nude mice. AC-73 inhibits the phosphorylation of ERK1/2 and STAT3 in a dose-dependent manner. MMP-2 is also reduced by AC-73. AC-73 could not inhibit tumor cell proliferation in vivo[1]. Animal Model: Male BALB/c nu/nu mice (4-6 weeks) with SMMC-7721 cells[1]
[1]. Fu ZG, et al. A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells. Oncotarget. 2016 Feb 23;7(8):9429-47. [2]. Spinello I, et al. The small-molecule compound AC-73 targeting CD147 inhibits leukemic cell proliferation, induces autophagy and increases the chemotherapeutic sensitivity of acute myeloid leukemia cells. Haematologica. 2019 May;104(5):973-985.
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