TABLE 2.
Other small-molecule compounds for inhibiting autophagy in cancer therapy.
| Compound | Mechanism | Cancer | Biological activity | Ref. |
|---|---|---|---|---|
| Hydroxychloroquine | Impairing autophagosome fusion with lysosomes | Breast cancer/pancreatic cancer/colon cancer/renal cancer/melanoma | IC50 = 15–42 μM | Takhsha et al. (2021) |
| Chloroquine | Impairing autophagosome fusion with lysosomes/increasing cytotoxicity by decreasing proliferation and inducing cell apoptosis via the induction of p21WAF1/CIP1expression and autophagy inhibition | Pancreatic adenocarcinoma/triple-negative breast cancer | EC = 15 µM | Liu et al. (2018), Mauthe et al. (2018) |
| Mefloquine | Inhibiting glioblastoma angiogenesis via disrupting lysosomal function/inhibiting NF-κB signaling and inducing apoptosis | Breast cancer/glioblastoma/colorectal cancer | EC = 0.5 µM | Hwang et al. (2020) |
| EC/ECCQ = 30 | ||||
| Lys05 | Suppressing autophagy by phosphorylating p62 and AKT1S1 | Lung cancer | IC50 = 3.6 µM | Sharma et al. (2012), Liang et al. (2016) |
| VATG-027 | Sensitizing melanoma tumor to vemurafenib by lysosomal deacidification and disruption of autophagosome | Melanoma | IC50 = 0.7 µM | McAfee et al. (2012); Ondrej et al. (2020) |
| EC = 0.1 µM | ||||
| VATG-032 | Sensitizing melanoma tumor to vemurafenib by lysosomal deacidification and disruption of autophagosome | Melanoma | IC50 = 27 µM | McAfee et al. (2012); Ondrej et al. (2020) |
| EC = 5 µM | ||||
| Nitazoxanide | Blocking late-stage lysosome acidification | Glioblastoma | IC50 = 383.4–659.9 μM | Goodall et al. (2014) |
| Dimeric quinacrine 661 (DQ661) | Inhibiting autophagy by targeting palmitoyl-protein thioesterase 1 (PPT1) | Melanoma/pancreatic cancer | IC50 = 15 μM | Zhao et al. (2020) |
| ROC-325 | Inhibiting ATG5/7-dependent autophagic degradation and inducing apoptosis | Renal cell carcinoma | IC50 = 4.9 µM | Rebecca et al. (2017), Wang et al. (2018), Jones et al. (2019) |
| CA-5f | Suppressing autophagosome–lysosome fusion/exhibiting strong cytotoxicity by increasing mitochondrial-derived reactive oxygen species (ROS) production | Lung cancer | IC50 = 20 μM | Carew et al. (2017) |
| IITZ-01 | Potentiating TRAIL-induced apoptosis by DR5 upregulation and survivin downregulation via ubiquitin–proteasome pathway | Renal cancer/lung cancer/triple-negative breast cancer | IC50 = 2.6 μM | Carew and Nawrocki (2017), Zhang et al. (2019) |
| Tenovin-6 | Affecting the acidification of autolysosomes and hydrolytic activity of lysosomes | Leukemia | IC50 = 9.6 ± 0.8 μM | Guntuku et al. (2019) |
| TN-16 | Blocking autophagosome–lysosome fusion | Breast cancer | IC50 = 0.4–1.7 uM | Shahriyar et al. (2020) |
| Cepharanthine | Blocking autophagosome–lysosome fusion and inhibiting lysosomal cathepsin B and cathepsin D maturation | Non-small cell lung cancer/breast cancer | IC50 = 3.6 uM | Yuan et al. (2017) |
| Verteporfin | Inhibiting PD-L1 through autophagy and the STAT1–IRF1–TRIM28 signaling axis/inducing p53 and impairing ubiquitin proteasomal degradation pathway (UPS) | Pancreatic ductal adenocarcinoma/osteosarcoma | IC50 = 2.1–5.6 uM | Donohue et al. (2011), Young et al. (2018), Hasanain et al. (2020) |
| PHY34 | Inhibiting autophagy by targeting the ATP6V0A2 subunit while interacting with cellular apoptosis susceptibility and altering nuclear localization of proteins | Ovarian cancer/breast cancer | HGSOC cell IC50 = 4 nM | Tang et al. (2018), Liang et al. (2020) |
| MDA-MB-435 IC50 = 23 nM | ||||
| MDA-MB-231 IC50 = 5.2 nM | ||||
| Celecoxib | Inhibiting cancer cell growth by modulating apoptosis and autophagy and reducing migration | Acute leukemia/osteosarcoma | IC50 = 40 nM | Saini et al. (2021) |
| Bafilomycin A1 | Preventing the fusion of autophagosome and lysosome/suppressing the degradation of protein in autolysosome | Leukemia | IC50 = 4–400 nM | Salvi et al. (2022) |