TABLE 2.
HIF-1α inhibitors under investigation in BC.
| Compound | Dose | HIF-1 activity IC50 | Cell growth inhibition IC50 | Model | Duration of treatment | Routes of administration | Type of study | Mechanism | Results | References |
|---|---|---|---|---|---|---|---|---|---|---|
| KC7F2 | 40 uM | 15 uM | 20 uM | MCF-7 | 8–72 h | — | in vitro | decrease HIF-1a protein accumulation | Inhibit cancer cell growth in a dose-independent manner | Narita et al. (2009) |
| LXY6090 | 0.4 nM-100uM | 4.11 ± 0.4 nM | T47D: 245.7 ± 15.2 nM; MCF-7: 352.7 ± 14.2 nM; MX-1: 108.2 ± 2.1 nM | T47D, MCF-7, MX-1 | 16–96 h | — | in vitro | downregulate HIF-1a protein and mRNA level by promoting HIF-1a proteasome degradation | Inhibit breast cancer cells growth dose-dependently | Lai et al. (2016) |
| 25 mg/kg/d to 100 mg/kg/day | — | — | Mouse model (MX-1) | 14 days | ip | in vivo | depress HIF-1a expression in vivo | Inhibit MX-1 cells subcutaneous xenograft tumors growth in a dose dependent manner | ||
| Quercetin | 10–100 uM | — | — | SkBr3 | 1–8 h | — | in vitro | inhibiting HIF-1a protein accumulation | Did not affect cancer cell activity | Lee and Lee, (2008) |
| Aryl Carboxamide Derivatives (30 m) | 0.5–30 uM | 0.32 uM | — | MDA-MB-231 | 24 h | — | In vitro | inhibit HIF-1a protein accumulation and promote its degradation | Suppress cancer cells angiogenesis activity dose-dependently, and inhibit cancer cell invasion and migration | Liu et al. (2019) |
| 15–30 uM/2 days | — | — | Mouse model (MDA-MB-231) | 3 weeks | ig | in vivo | inhibit HIF-1a protein accumulation | Inhibit lung colonization of tumor cells without obvious body weight loss in a dose-depended manner | ||
| LXY6006 | 0.1–1 uM | 0.35 ± 0.11 nM | 1.3–249.7 nM | T47D, MD-MBA-231, MX-1 | 4–5 days | — | in vitro | inhibit HIF-1a nuclear accumulation | Arrest cell cycle, and hold back cancer cells growth | Lang et al. (2014) |
| LXY6006 | 60 or 120 mg/kg/6 days per week | — | — | Mouse model (MX-1 or MX-1/Taxol) | 13 days | ig | in vivo | — | Arrest both normal and taxol-resistant breast cancer xenograft growth with slight body weight loss | |
| Aminoflavone | 0.06-1uM | — | — | MCF-7 | 16 h | — | in vitro | depress HIF-1a protein accumulation and decreases the rate of HIF-1α translation | Shows cytotoxic effect on breast cancer cells | Terzuoli et al. (2010) |
| Aminoflavone | 60 mg/kg/day | — | — | Mouse model (MCF-7) | 4 days | — | in vivo | AF inhibits HIF-1α expression | Inhibit cancer growth | |
| 7-Hydroxyneolamellarin A | 0.6–50 μmol/L | 23.0 ± 2.6 μmol/L | — | MCF-7,4T1 | 4–36 h | — | in vitro | inhibit HIF-1a protein accumulation | Suppress the cellular migration, invasion and proliferation dose-dependently | Li et al. (2021) |
| 7-Hydroxyneolamellarin A | 15 mg/kg/2 days | — | — | Mouse model (4T1) | 23 days | — | in vivo | inhibit HIF-1a protein accumulation | Inhibit HIF-1a and breast tumor growth with slightly body weight effect | Li et al. (2021) |
| DJ12 | 2.5–100 uM | 3.6 uM | 165–250 uM | MDA-468, ZR-75, MD435 | 16 h | — | in vitro | decrease HIF-1a transactivation and DNA binding | — | Jones and Harris, (2006) |
| Cardenolides | — | 21.8–64.9 nM | 30.5–68.8 nM | MCF-7 | 24 h | — | in vitro | inhibited HIF-1 transcriptional activity dose-dependently | cytotoxic effects on breast cancer cells | Parhira et al. (2016) |
| PX-478 | — | — | — | Mouse model (MCF-7) | — | — | in vivo | suppresses HIF-1a levels | antitumor activity | Welsh et al. (2004) |
| Methylalpinumisoflavone | 0.01–10 uM | 0.6 μM | — | T47D, MDA-MB-231 | 24–48 h | — | in vitro | inhibits HIF-1 activation by blocking the induction of nuclear HIF-1α protein | Inhibit tumor angiogenesis in vitro, cell migration, and chemotaxis | Liu et al. (2009) |