Table 5.
Inhibitors directly targeting the HIF pathway in cancers.
| Mechanism of inhibition | Compound/drug name | Current status | Tumor type |
|---|---|---|---|
| Inhibit HIF-1α mRNA expression | EZN-2698 | I | Advanced malignancies (236) |
| Inhibit HIF-1α protein expression | Digoxin | II | Biochemically relapsed prostate cancer (237) |
| 2-methoxyestradiol | II | Multiple types of cancer (238) | |
| PX-478 | I | Advanced solid tumors and lymphomas (239) | |
| Increased HIF-1α degradation | YC-1 | Preclinical | Several solid tumors (240) |
| PX-12 | II | Previously treated advanced pancreatic cancer (241) | |
| LW6 | Preclinical | Colon cancer (242) | |
| Inhibit HIF heterodimerization | Acriflavin | Preclinical | Prostate cancer (226) |
| PT-2385 | I | Advanced clear cell renal cell carcinoma (243) | |
| PT-2399 | Preclinical | pVHL-defective clear cell renal cell carcinoma (244) | |
| Inhibit HIF-1/DNA binding | Echinomycin | II | Several advanced cancers (245–249) |
| Inhibit HIF-1 transcriptional activity | Chetomin | Preclinical | Multiple myeloma (250) |
| Bortezomib | FDA approved | Multiple myeloma and several solid tumors (251) | |
| Vorinostat | II | Metastatic urothelial cancer (252) |