TABLE 3.
Dual and multiple targeted small-molecule compounds for inhibiting autophagy in cancer.
| Target | Compound | Mechanism | Cancer | Biological activity | Ref. |
|---|---|---|---|---|---|
| PI3K/mTOR inhibitor | PKI-402 | Suppressing cancer cell growth by degradation of Mcl-1 protein and disruption of the balance of Bcl-2 family protein | Ovarian cancer | IC50 = 2–16 nM | Lu et al. (2016) |
| PI3K/mTOR inhibitor | CMG002 | Inducing G0/G1 cell cycle arrest and enhancing apoptotic cell death | Gastric cancer | AGS IC50 = 1.6 uM | Fischer et al. (2020), Hu et al. (2020) |
| NUGC3 IC50 = 4.9 uM | |||||
| Hsp90 and late-autophagy inhibitor | DCZ5248 | Inducing lysosomal acidification and lysosomal cathepsin activity/inducing G1-phase cell cycle arrest and apoptosis | Colon cancer | IC50 = 0.5 uM | Kim et al. (2019) |
| AMPK and Rab7 prenylation inhibitor | N6-isopentenyladenosine (iPA) | Impairing autophagic flux by blocking autophagosome–lysosome fusion through the defective function of Rab7 | Melanoma | IC50 = 2.5 μM | Choi et al. (2019) |
| PI3K/mTOR inhibitor | NVP-BEZ235 | Sensitizing cancer cells to radiotherapy through G2/M arrest and apoptotic cell death | Glioblastoma multiforme/thyroid cancer | IC50 = 38.9 nM | Ranieri et al. (2018), Chen X. L. et al. (2021) |
| PI3K/Akt/mTOR inhibitor | PI103 | Inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways in prostate cancer | Cancer | IC50 = 30 nM | Zhu et al. (2013) |
| HER2 inhibitor | TAK-165 | Inhibiting autophagy in a HER2-independent manner | Acute myelocytic leukemia | IC50 = 6 nM | Chang et al. (2013) |
| CDK7 inhibitor | THZ1 | Enhancing cytotoxicity via autophagy suppression | Renal cell carcinoma | IC50 = 3.2 nM | Chang et al. (2014) |
| CD13 inhibitor | Ubenimex | Sensitizing cancer cells to CDDP by autophagy through perturbing the CD13/EMP3/PI3K/AKT/NF-κB axis | Gastric cancer | IC50 = 20 μM | Huang et al. (2019) |
| JNK inhibitor | SP600125 | Sensitizing cancer cells to oxaliplatin by inhibiting autophagy | Colorectal cancer | IC50 = 40 nM | Chen H. et al. (2021) |
| Lysosome inhibitor | Trifluoperazine | Inhibiting autophagy flux by impairing lysosomes acidification and decreasing protein level of cathepsin L | Glioblastoma | IC50 = 15 μM | Guo et al. (2019) |
| MEK/ERK inhibition | Lycorine | Enhancing the degradation of high mobility group box 1 (HMGB1)/suppressing MEK-ERK pathway and increasing Bcl-2–Beclin-1 interaction | Multiple myeloma | IC50 = 20 μM | Vasilevskaya et al. (2016) |