Table 5.
Summary of related drugs/inhibitors targeting HIF-1α.
| S.No. | Agents | Mechanism of action | Target gene/ Signaling |
Therapeutic strategies | Pre-clinical/Clinical trial status | References |
|---|---|---|---|---|---|---|
| 1. | Acriflavine | Inhibits premetastatic niche of TNBC by blocking HIF-1α | HIF-1α/LOX | Monotherapy | Preclinical | (97, 320) |
| 2. | As4S4 | Inhibits the TNBC metastasis by scavenging ROS and reduce thr transcription level of HIF-1α | ROS/HIF-1α | Monotherapy | Preclinical | (97, 321) |
| 3. | Cardamonin | Inhibits the transcription of HIF-1α | mTOR/P70s6k/HIF-1α | Monotherapy | Preclinical | (97, 322) |
| 4. | Digoxin (DIG) | Blocks the accumulation of HIF-1α and HIF-2α in hypoxic cells and block chemotherapy-induced expression of IL-6, IL-8, and MDR-1, and blocked BCSC enrichment | HIF-1α/VEGF | Monotherapy | Preclinical | (318) |
| 5. | Diallyl Trisulfides (323) | Inhibits the translation level of HIF-1α and inhibits the TNBC metastasis | HIF-1α | Monotherapy | Preclinical | (97, 324) |
| 6. | Elemene (C15H24) | Reduce the stability of HIF-1α | ROS/HIF-1α | Monotherapy | Preclinical | (97, 325) |
| 7. | Ganetespib | Induces the HIF-1α protein degradation and controls the angiogenesis, metabolism, invasion, and metastasis in TNBC | Hsp90/HIF-1α/SDF1/VEGF/GLUT1, HK2/PDK1/ALD1A1, ALD1A3/MMP9 /P4HA1/P4HA2/ANGPTL4/ LICAM/LOX |
Monotherapy | Preclinical/II | (97, 326) |
| 8. | Isoliquiritigenin (ILTG) | Inhibits the expression of HIF-1α and VEGF and inhibits the TNBC metastasis | PI3K/Akt/HIF-1α/VEGF//NF-κB | Monotherapy | Preclinical | (327) |
| 9. | Nanoliposomal echinomycin | Blocks the activity of HIF-1α | HIF-1α/VEGF | Monotherapy | Preclinical | (97, 328) |
| 10. | Melittin | Inhibits the transcription of HIF-1α by inhibiting NF-κB expression | HIF-1α/VEGFA/ NF-κB/LDHA |
Monotherapy | Preclinical | (328) |
| 11. | Sanguinarine | Induces the proteasomal degradation of HIF-1α | HIF-1α/STAT3 blocker | Monotherapy | Preclinical | (329) |
| 12. | Amphotericin B | Suppress the binding of HIF-1α/p300 complex to HRE | HIF-1α/p300/FIH1 and PI3K/mTOR | Monotherapy | Approved for clinical use | (320, 330) |
| 13. | Apigenin | Inhibits expression of HIF-1α and VEGF | PI3K/AKT/p70S6K1 and HDM2/p53 | Monotherapy | II | (331) |
| 14. | YC-1 | Inhibits HIF-1α synthesis and blocked angiogenesis and an inhibition of tumor growth | HIF-1α | Monotherapy | Preclinical | (332) |
| 15. | Pleurotin (PX-12) | Inhibits the proto-oncogene (Trx-1) which further blocks the activity of HIF-1α | Trx-1 and thioredoxin 1 | Monotherapy | II | (333) (334) |
| 16. | Polyamides | Modulates the HIF-1alpha activity at transcriptional level | HIF-1α | Monotherapy | N/A | (335) |
| 17. | 2-phenethyl isothiocyanate (PEITC) | Down-regulates theHIF-1α with reduction of ROS and by induction of Nrf2 signaling | HIF-1α/Nrf2/MMPs 2 & 9/VEGF | Monotherapy | II | (320, 336) |
| 19. | PX-478 | Inhibits the expression of HIF-1α and HIF-1 transcription factor activity | HIF-1α/VEGF/GLUT-1 | Monotherapy | I | (337) |
| 20. | Silibinin | Inhibits the HIF-1α synthesis and induces the metabolic crisis in triple-negative breast cancer cells by modulating EGFR-MYC-TXNIP axis | mTOR/p70S6K/4E-BP1 | Monotherapy | Approved | (338) |
| 21. | Wondonin | Induces the proteasomal degradation of HIF-1α by increasing the interaction of HIF-1α and pVHL | HIF-1alpha/pVHL/ERK1/2//Akt | Monotherapy | Preclinical | (339) |
| 22. | Sulphoraphane | Decrease the HIF-1α and VEGF expression by inhibition of STAT3/HIF-1α/VEGF signaling | HIF-1α | Monotherapy | II | (340) |
| 23. | Cardenolides | Inhibits the expression of HIF-1α and HIF-1 transcription factor activity | HIF-1α | Monotherapy | Approved for clinical use | (341) |
| 24. | DIM (3,3’-Diinolylmethane) | Downregulates the mRNA expression of HIF-1α | HIF-1α/TRAF2/p38 MAPK | Monotherapy | III | (342) |
| 25. | Pseudolaric acid (186) | Inhibits angiogenesis and reduces HIF-1α by promoting proteasome-mediated degradation | JNK/SAPK and p53 and HIF-1α/VEGF/KDR | Monotherapy | Preclinical | (343) |
| 26. | Andrographolide | Suppress COX-2 expression and angiogenesis via inactivation of HIF-1α/p300 signaling and VEGF pathway | HIF-1α/p300/VEGF | Monotherapy | III | (344) |
| 27. | Curcumin | Inhibits the expression of HIF-1α and HIF-1 transcription factor activity by degrading ARNT in cancer stem-like cells and reduces the proliferation and metastasis of TNBC cells | Hedgehog/Gli1/HIF-1α | Monotherapy | II | (345) |
| 28. | Echinomycin | Inhibits HIF-1α transcriptional activity of primary and metastatic TNBC cells | HIF-1α | Monotherapy | Rejected after Phase II trial | (328) |
| 29. | Flavopiridol (alvocidib) | Inhibiting HIF-1α gene transcription | HIF-1α | Monotherapy | III | (346) |
| 30. | GA and analogs | Induces the proteasomal degradation of HIF-1α | HIF-1α/Hsp90 | Monotherapy | II | (347) |