HIF1’s regulatory mechanism | More detailed mechanism | Agents | Current study phase | Clinical trial identifier | Refs. |
---|---|---|---|---|---|
Transcriptional level | NS | Alvocidib (Flavopiridol) | II | NCT00445341 | |
Translational level | Antisense oligonucleotide | EZN-2968 | I | NCT01120288 NCT02564614 | |
RX-0047 | None | NS | [293] | ||
Blocking mTOR/p70S6K/4E-BP1 pathway | Silibinin | II | NCT00487721 NCT01129570 NCT06187220 | ||
KC7F2 | None | NS | [296] | ||
PI3K inhibitors | Buparlisib | III | NCT04338399 | ||
Blocking mTOR | Rapamycin | Approved | NCT03500367 | [299] | |
Everolimus | Approved | NCT02842749 | [300] | ||
Temsirolimus/CCI-779 | Approved | NCT03500367 | [301] | ||
ATR inhibition | AZD6738 | II | NCT05514132 | ||
VX-970 (M6620) | II | NCT03718091 | |||
Microtubule depolymerization | 2ME2 and ENMD-1198 | II | NCT00592579 NCT00444314 | ||
Inhibiting HIF-1α mRNA translation | 2-Phenethyl isothiocyanate | II | NCT00691132 | [307] | |
Inhibiting Na+/K+ ATPase | Digoxin | I/II | NCT06030622 | ||
PHDs | Possibly zinc deprivation | Metallothioneins (MTs) | None | NS | [253] |
Promoting the interaction between HIF1 and PHD | GYY4137 | None | NS | ||
Ubiquitination | Related to proteasome | Cetuximab | Approved | NCT00044863 NCT00392769 | [255] |
Inducing pVHL expression | LW6 | None | NS | [311] | |
Increasing HIF-1a and pVHL interaction | Wondonin | None | NS | [312] | |
Trans-activation | Hsp90 inhibition | Lonafarnib | III | NCT00773474 NCT00050336 | [257] |
GA (geldanamycin) and analogs/tanespimycin | II | NCT00093405 NCT00087386 | |||
Ganetespib | III | NCT01562015 NCT01039519 | |||
Apigenin | II | NCT00609310 | [316] | ||
Radicicol and its derivatives | None | NS | |||
HDAC inhibition | SAHA and FK228 (vorinostat and romidepsin) | Approved | NCT00801151 | ||
Trichostatin A (TSA) | I | NCT03838926 | [319] | ||
LAQ824 | None | NS | [320] | ||
Inhibiting FIH-1 or the p300 recruitment | Bortezomib | Approved | NCT00512798 | [262] | |
Amphotericin B | None | NCT01615809 | [263] | ||
Chetomin | None | NS | [321] | ||
Disturbing HIF1-HRE binding | Anthracycline | Approved | NCT04182568 | [264] | |
Polyamides | None | NS | [322] | ||
Echinomycin (NSC-13502) | None | NS | |||
Inhibiting the recruitment of RNA polymerase II | Metformin | None | NCT05921942 NCT03684707 | ||
Disturb the dimerization of HIF-1α and HIF-1β | Anti-HIF-1a VHH and hetero-bivalent VHH nanobodies (AG1-5) | None | NS | [267] | |
Acriflavine | None | NS | |||
Multitarget medicines | Inhibiting transcriptional initiation of the HIF-1α gene Suppressing transactivation activity of HIF-1α protein Disturbing the dimerization of HIF-1α and HIF-1β | Aminoflavone (AF) | II | NCT01015521 | |
HIF-1α translation HIF-1α protein accumulation HIF-1 transcriptional activity | Camptothecin analogs (TPT, EZN-2208) | II | NCT01601184 NCT01036113 | ||
Increasing pVHL activity Activating PHDs’ activity Impairing HIF-1 protein translation | Melatonin, NB-5-MT | None | NCT04137627 NCT04530097 |