Table 1.
Classification of molecules intervening HIF-1α pathway according to their putative mechanisms of action.
| Mechanism of inhibition | Inhibitor | Target | ||
|---|---|---|---|---|
| HIF-1α mRNA expression | EZN-2698 (1) | HIF-1α mRNA | ||
| Aminoflavone (2) | ||||
| HIF-1α translation | CPTs (3): | Topoisomerase I | ||
| topotecan (3a), EZN-2208 (3b), SN38 (3c), irinotecan (3d) | ||||
| Temsirolimus (4) | mTOR | |||
| Everolimus (4a) | ||||
| Sirolimus (4b) | ||||
| LY294002 (5) | PI3K | |||
| Wortmannin (6) | ||||
| Cardiac glycosides (7): | HIF-1α protein/HIF-2α mRNA | |||
| digoxin (7a), ouabain (7b), proscillaridin (7c) | ||||
| 2ME2’s (8): | Microtubules | |||
| 2ME2 (8a), ENDM-1198 (8b), ENMD-1200 (8c), ENMD-1237 (8d) | ||||
| HIF-1α stabilization | GAs (9): | Radicicol (10a), KF58333 (10b) | SCH66336 (11), Apigenin (12) | Hsp90 |
| GA (9a), | ||||
| 17-AAG (9b), | ||||
| 17AG (9c), | ||||
| 17-DMAG (9d) | ||||
| Romidepsin (KF228) (13) | HDAC | |||
| Trichostatin (14) | ||||
| LW6 (15) | HDAC/VHL | |||
| HIF-1α dimerization | Acriflavin (16) | PAS-B | ||
| HIF-1/DNA binding | Echinomycin (17) | 5′-CGTG-3′ | ||
| Anthracyclines (18): doxorubicin(18a), danuorubicin(18b) | HRE | |||
| HIF-1 transcriptional activity | Chetomin (19) | CH1 domain of p300 | ||
| Bortezomib (20) | C-TAD of HIF-1α and Asn803 of FIH | |||
| HIF-1α at multiple levels | YC-1 (21) | HIF-1&2 protein/FIH | ||
| PX-478 (22) | HIF-1&2 protein | |||