Table 2: Autophagy can be targeted through a variety of small molecule inhibitors.
Literature search found a variety of small molecule compounds can target autophagy at various stages of the process. Autophagy can be targeted via PI3K/mTOR, Beclin, BCL2, lysosomal cellular components or p62. Targeting can either be beneficial (anti-cancerous) or harmful (precancerous) depending on the subtype of gastric cancer and the driver mutations within the tumor. Many compounds have been tested in clinical trials in various solid tumors but further work needs to be done to elucidate the effect specifically in gastric cancer.
| AUTOPHAGY TARGET GENE | COMPOUND | CLINICAL TRIAL VIA CLINICALTRIAL.GOV |
|---|---|---|
| Beclin-1/PI3KCIII/VSP34 | Spautin-1 | No- Preclinical176 |
| Beclin-1/INS (1, 4, 5) P3 | Xestosponging B | No- Preclinical 176 |
| Beclin-1 | Tat-beclin 1 (Tat-BECN1) | No |
| p62/FOXO3A | Selinexor | Planned |
| mTOR1/2 | Everolimus | Yes (22 Studies GC) 193 |
| mTOR1/2 | Temsirolimus | Yes (21 Studies GC) 193 |
| mTOR | CC-223 (Onatasertib) | |
| PI3K/mTOR | BMK120 | Yes (Breast Only) |
| PI3K/mTOR | PX-886 | No |
| PI3K/mTOR | XL 147 | Yes (Various Solid Tumors) |
| PI3K/mTOR | WX-037 | Yes (Various Solid Tumors) |
| PDK/mTOR | BYL719 | Yes (1 GC) |
| PDK/mTOR | GDC0032 | Yes (1 GC) |
| PDK/mTOR | INK1117 | Yes (Various Solid Tumors) |
| PI3K/mTOR | P7170 | Yes (Refractory Solid Tumors) |
| PI3K/mTOR | BEZ235 | Yes (Malignant Solid Tumors) |
| PI3K/mTOR | XL765 | Yes (Various Solid Tumors) |
| P13K/mTOR | GDC-0980 | Yes (Breast, NHL, Renal, Endometrial) |
| PI3K/mT0R | SF1126 | Yes (Advanced Metastatic Tumors) |
| PI3K/mT0R | PF-05212384 | Yes (Various Solid Tumors) |
| PI3K/mT0R | PF-4691502 | Yes (Breast Cancer) |
| PI3K/mT0R | VS-558 | No |
| P13K/mTOR | OSI-027 | Yes (Various Solid Tumor/Lymphoma) |
| P13K/mTOR | AZD2014 | Yes (2 Studies GC) |
| P13K/mTOR | AZD8055 | Yes (Various Solid Tumors) |
| P13K/mTOR | MK-2206 | Yes (2 Studies GC) |
| PI3K/mT0R | AZD5363 | Yes (2 Studies GC) |
| PI3K/mT0R | GSK690693 | Yes (2 Hematological Malignancies) |
| PI3K/mT0R | GDC0068 | Yes (2 Studies GC) |
| PI3K | Salidroside | No- Preclinical 204 |
| P13K/mTOR | B-elemene | No- Preclinical 205 |
| P13K/mTOR | B-elemene | No- Preclinical 205 |
| AMPK Phosphorylation | Chichoric acid | No- Preclinical 206 |
| AMPK phosphorylation | Perillaldehyde | No- Preclinical |
| ULK1 | LYN-1604 | No- Preclinical 229 |
| ULK1/ULK2 | SBI-0206965 | No- Preclinical 229 |
| ULK1 | MRT68921 HCL | No- Preclinical 229 |
| ULK1/ULK2 | ULK-101 | No- Preclinical 229 |
| ATG4B | NSC185058 | No- Preclinical 230 |
| ATG4B | Flubendazole | No- Preclinical 230 |
| Lysosome | DC661 | No- Preclinical 231 |
| Lysosome | Lys05 | No- Preclinical 231 |
| Lysosome/PI3K/mTOR | Hydroxychloroquine | No- Preclinical 232 |
| Autophagosome/Lysosome | CA-5f | No |
| Lysosome | Eliglustat | Yes (Gaucher Disease) |
| Autophagy/mitophagy | Liensinine | No- Preclinical 233 |
| PERK | GSK2606414 | No- Preclinical 234 |
| PERK | GSK2656157 | No- Preclinical 235 |
| PERK | ISRIB (Trans-isomer) | No |
| ROS | Acetylcysteine (N-Acetylcysteine) | No- Preclinical 236 |
| BCL2 | Venetoclax (ABT-199) | Yes (Solid Tumors/1 GC) |
| BCL-2 | TW-37 | No- Preclinical 237–238 |
| BCL-2 | BH3I-1 | No |
| BCL-2 | S63845 | No- Preclinical 239 |
| BCL-2 | HA14–1 | No- Preclinical 240 |
| BCL-2 | Navitoclax (ABT-263) | Yes- (Solid Tumors) |
| BCL-2 | ABT-737 | No- Preclinical 241–242 |
| BCL-2/p53 | Pifithrin-u | No- Preclinical 243 |