LW6

SKU: orb1222984

Description

CAY10585, also known as LW6, was first identified and reported by a group scientists from Korea. LW8 was found to inhibits the accumulation of HIF-1alpha. LW6 decreased HIF-1alpha protein expression without affecting HIF-1beta expression. It was further found that LW8 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 the presence of LW8, knockdown of VHL did not abolish HIF-1alpha protein accumulation, indicating that LW8 degraded HIF-1alpha via regulation of VHL expression. In mice carrying xenografts of human colon cancer HCT116 cells, LW8 demonstrated strong anti-tumor efficacy in vivo and caused a decrease in HIF-1alpha expression in frozen-tissue immunohistochemical staining. These data suggest that LW8 may be valuable in the development of a HIF-1alpha inhibitor for cancer treatment.

Key Properties

• CAS Number: 934593-90-5
• MW: 435.52
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₉NO₅
• SMILES: O=C(OC)C1=CC=C(O)C(NC(COC2=CC=C(C3(C4)CC5CC4CC(C5)C3)C=C2)=O)=C1
• Target: HIF-1
• Solubility: DMSO : ≥ 33 mg/mL; 75.77 mM

Bioactivity

• In Vivo:
  In mice carrying xenografts of human colon cancer HCT116 cells, LW6 demonstrates strong anti-tumor efficacy In vivo and causes a decrease in HIF-1α expression in frozen-tissue immunohistochemical staining.
• In Vitro:
  LW6 affects the stability of the HIF-1α protein. LW6 promotes the degradation of wild type HIF-1α, but not of a DM-HIF-1α with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain. LW6 induces the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1α for proteasomal degradation. In the presence of LW6, knockdown of VHL does not abolish HIF-1α protein accumulation, indicating that LW6 degraded HIF-1α via regulation of VHL expression. In MDCKII-BCRP cells overexpressing BCRP, LW6 enhances significantly the cellular accumulation of mitoxantrone, a BCRP substrate. LW6 also down-regulates BCRP expression at concentrations of 0.1-10 μM. LW6 inhibits the expression of HIF 1α induced by hypoxia in A549 cells at 20 μM, independently of the von Hippel Lindau protein. LW6 induces hypoxia selective apoptosis together with a reduction in the mitochondrial membrane potential.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CAY10585 | CAY-10585 | CAY 10585 | LW6

Quick Database Links

Gene Symbol

HIF-1