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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 |
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