Table 4.
Small-Molecule Inhibitors Target Extracellular Matrix Components
| Target | Small-molecular Inhibitor | Target Strategy | Mechanism of Action | Cancer Target | References |
|---|---|---|---|---|---|
| Hyaluronan (HA) | 4-methylumbelliferone (MU) | Lower HA levels | Inhibit HAS to synthesize HA | Prostate, breast, pancreatic cancer | [[147], [148], [149]] |
| Matrix metalloproteinases (MMPs) | cis-ACCP | Inhibit MMPs and show antimetastatic activity | Sustain and prolong absorption occurred via paracellular | Prostate and melanoa cancer | [150] |
| N-[4-(difluoromethoxy)phenyl]-2-[(4-oxo-6-propyl-1Hpyrimidin-2-yl)sulfanyl]-acetamide | Abrogate MMP-9 homodimerization and block MMP-9–mediated cell migration related signaling pathway | Target hemopexin (PEX) domain of matrix metalloproteinase-9 | Breast cancer | [151] | |
| Lysophosphatidic acid (LPA) | ONO-8430506 | Decrease lysophosphatidate signaling | Inhibit activity of secreted enzyme, autotaxin (ATX) | Breast cancer | [152] |
| PF-8380 | Abrogate radiation-induced tumor neovascularization and delay tumor growth | Inhibit activity of secreted enzyme, autotaxin (ATX) | Glioblastoma multiforme | [153] | |
| Collagen | 3-[4″-methoxy-3,2′-dimethyl-(1,1'; 4′,1″)terphenyl-2″-yl]propionic acid (T12) | Impair the formation of mesh collagen IV and impede tumor EMT | Target mesenchymal goodpasture antigen-binding protein (GPBP) and disturb its multimerization | Non-small cell lung carcinoma (NSCLC) | [154] |