Table 2.
Potential HIF-1 inhibitors under development.
| HIF-1 Inhibitors | Animal Models | Clinical Trials | References |
|---|---|---|---|
| Transcriptional initiation | |||
| Flavopiridol | No animal model looking at effect on hypoxia/HIF-1 | Not in clinical use | [35,36,37,38,39] |
| Aminoflavone (AF) | MCF-7 xenografts | Phase 1 (Completed) | [40,41,42,43] |
| mRNA stabilization | |||
| EZN-2968 | DU145 xenograft | Phase 1 (Completed) | [44,45] |
| Translational initiation | |||
| Rapamycin | LKB1 ± mice (Peutz-Jeghers syndrome model), ACHN xenograft, SN12C xenograft | FDA-approved for treatment for renal cell carcinoma (RCC) | [46,47,48] |
| Cetuximab | Tgfb1/Pten deletion 2cKO mice, CAL27 xenograft | FDA-approved for head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) | [49,50] |
| Buparlisib | No animal model looking at effect on hypoxia/HIF-1 | Phase 3 (Completed, Terminated) | [51] |
| KC7F2 | No animal model looking at effect on hypoxia/HIF-1 | Not in clinical use | [52] |
| 2-MEs | LLC xenograft/MDA-MB-231 xenograft | Phase 2 (Completed) | [53,54,55,56,57] |
| Digoxin | P493 xenograft/PC3 xenograft | Phase 2 (Completed, Terminated) | [58,59] |
| AZD6738, VX-970 | OE21 xenograft (VX-970) | AZD6738: Phase 2 (In progress) | [60] |
| VX-970: Phase 2 (In progress) | |||
| Protein stabilization | |||
| Melatonin, NB-5-MT | Tumor xenograft models with breast, kidney, prostate, and colon cancer cells in mouse and zebrafish | Not in clinical use | [61,62,63,64,65,66] |
| LW6 | HCT116 xenograft | Not in clinical use | [67] |
| GYY4137 | No animal model looking at effect on hypoxia/HIF-1 | Not in clinical use | [68,69] |
| Ganetespib | Orthotopic implantation of MDA-MB-231, MDA-MB-435 | Phase 2 (Completed) Phase 3 (Terminated) |
[70,71,72,73] |
| Apigenin | PC-3 and OVCAR3 Matrigel plug assay | Phase 2 (Terminated) | [74,75,76,77,78] |
| Lonafarnib | Orthotopic implantation of UMSCC38 | Phase 2 (Completed) Phase 3 (Terminated) |
[79,80,81,82,83] |
| Vorinostat | Hep3B xenograft | FDA-approved for cutaneous T-cell lymphoma Phase 2 with results for other cancer types |
[84,85,86] |
| Romidepsin (FK228) | Orthotopic implantation of LLC | FDA-approved for cutaneous T-cell lymphoma Phase 2 with results for other cancer types |
[87] |
| Trichostatin | No animal model looking at effect on hypoxia/HIF-1 | Phase 1 (In progress) | [88,89,90] |
| Heterodimerization | |||
| Acriflavine | PC-3 xenografts | Not in clinical use | [91,92,93] |
| DNA binding | |||
| Echinomycin | MDA-MB-231 and SUM-159 xenografts | Phase 2 (Completed) | [94,95,96,97,98] |
| Anthracycline | HeLa xenografts | Phase 2 (Completed) | [99] |
| Radicicol | No animal model looking at effect on hypoxia/HIF-1 | Not in clinical use | [100,101] |
| Transactivation | |||
| Bortezomib | SiHa xenografts | Phase 1 (Completed) | [102,103,104,105,106] |
| Other steps | |||
| PX-478 | HT-29 xenografts | Phase 1 (Completed) | [107,108] |
| Camptothecin analogues (TPT, EZN-2208) | U251 glioma xenografts | TPT: Phase 1 (Completed) | [109,110,111,112,113] |
| EZN-2208 combination with other drugs: Phase 1 (Completed) | |||
| CRLX101 | orthotopic primary triple-negative breast cancer xenografts | Phase 2 (Completed) | [114,115,116,117] |
| Metformin | Various types of tumors, e.g., CRC and HCC | Phase 3 (Completed) | [118,119,120,121] |
CTCL, cutaneous T-cell lymphoma.