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LW6 is a novel HIF-1alpha inhibitor, with an IC50 of 4.4 μM. LW6 decreases HIF-1α protein expression without affecting HIF-1β expression.
LW6 decreased HIF-1alpha protein expression without affecting HIF-1beta expression. LW6 promoted the degradation of wild type HIF-1alpha, but not of a DM-HIF-1alpha with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain (ODDD). LW6 did not affect the activity of prolyl hydroxylase (PHD), but induced the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1alpha for proteasomal degradation.
In mice carrying xenografts of human colon cancer HCT116 cells, LW6 demonstrated strong anti-tumor efficacy in vivo and caused a decrease in HIF-1alpha expression in frozen-tissue immunohistochemical staining.
| Molecular Weight | 435.51 |
| Formula | C26H29NO5 |
| CAS Number | 934593-90-5 |
| Solubility (25°C) | DMSO 25 mg/mL DMF 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related HIF Products |
|---|
| FG-4592 (Roxadustat)
FG-4592 (Roxadustat; ASP1517) is a novel Hypoxia Inducible Factor Prolyl Hydroxylase inhibitor. |
| 2-Methoxyestradiol
2-methoxyestradiol (2-ME2), an endogenous metabolite of 17β -estradiol (E2) with oral activity, is an apoptosis inducer and angiogenesis inhibitor with effective antitumor activity. Methoxyestradiol can also destabilize microtubules. Methoxyestradiol is a potent inhibitor of superoxide dismutase (SOD) and reactive oxygen species (ROS) that can induce autophagy in transformed cell line HEK293, cancer cell line U87 and HeLa. |
| DMOG
DMOG (Dimethyloxaloyl glycine) is an antagonist of α-ketoglutarate cofactor and a cell permeable and competitive inhibitor of HIF-PH, which results in HIF-1α stabilisation and accmulation in vitro and in vivo. DMOG acts as a pro-angiogenic agent and plays a protective role in experimental model of colitis and diarrhoea via HIF-1 related signal. DMOG induces cell autophagy. |
| IOX2
IOX2 is a potent inhibitor of HIF-1α prolyl hydroxylase-2 (PHD2) with IC50 of 21 nM, >100-fold selectivity over JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH. |
| Hydralazine hydrochloride
Hydralazine hydrochloride is a hydrochloride salt of hydralazine (Apresoline) that is a direct-acting smooth muscle relaxant with an IC50 of 1.9 mM. |
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