LW6

SKU: orb1304148

Description

LW6 is a novel small molecule inhibitor targeting hypoxia-inducible factor 1 alpha (HIF-1α). It is a valuable research tool for studying hypoxia signaling pathways in both cellular and animal models of cancer and ischemic diseases.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Metabolism Research

Key Properties

• CAS Number: 934593-90-5
• MW: 435.51
• Purity: 99.10%
• Formula: C₂₆H₂₉NO₅
• SMILES: COC(=O)c1ccc(O)c(NC(=O)COc2ccc(cc2)C2C3CC4CC(C3)CC2C4)c1
• Target: HIF/HIF Prolyl-Hydroxylase,Apoptosis,HIF,Dehydrogenase
• Solubility: 10% DMSO+90% Corn Oil:2.5 mg/mL (5.74 mM);DMSO:50 mg/mL (114.81 mM)

Bioactivity

• Target IC50:
  HIF:4.4 μM|MDH2:6.3 μM
• In Vivo:
  LW6 exhibits potent anti-tumor activity in vivo leading to reduced HIF-1α expression as observed through immunohistochemical staining of frozen tissues in mice with xenografts derived from human colon cancer HCT116 cell.
• In Vitro:
  LW6 decrease the expression of HIF-1α protein without affecting HIF-1β expression. LW6 affect the stability o the HIF-1α protein. LW6 promote the degradation of wild type HIF-1α while not of a DM-HIF-1α with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain. LW6 induce the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1α for proteasomal degradation the knockdown of VHL does not abolish HIF-1α protein accumulation in the presence of LW6 which indicates that LW6 degraded HIF-1α via regulation of VHL expressio. In MDCKII-BCRP cells overexpressing BCRP, LW6 enhances significantl the cellular accumulation of mitoxantrone, a BCRP substratee. LW6 also down-regulates BCRP expression at concentration of 0.1-10 μ. LW6 inhibit the expression of HIF 1α induced by hypoxia in A549 cells at 20 mM, independently o the von Hippel Lindau protein. LW6 induces hypoxia Selective apoptosis together with a reduction in the mitochondrial membrane potentia .
• Cell Research:
  Inhibition of HIF-1a is assayed by a Reporter assay using dualluciferase Reporter assay system. HCT116 cells in 75-90% confluence are transiently co-transfected with pGL3-HRE-luciferase Plasmid containing Six copies of HREs from human VEGF genes and pRLSV40 encoding firefly renilla luciferase and incubated for 24 h. Cells are treated with LW6 or 17-AAG for 16 h before report assay. Luciferase activity is integrated over a 10 second period and measured using a luminomete.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

MDH2, Inhibitor, HIF-1, HIF-1a inhibitor, HIF/HIF ProlylHydroxylase, HIF/HIF Prolyl-Hydroxylase, HIF/HIFProlylHydroxylase, HIF-1α inhibitor, HIF-1alpha inhibitor, HIF-PH, HIFProlylHydroxylase, HIFs, HIF, HIF ProlylHydroxylase, HIF Prolyl-Hydroxylase, Hypoxia-inducible factors, LW 6, LW 8, LW6, LW-6, LW8, LW-8, inhibit, CAY 10585, CAY10585, CAY-10585, Apoptosis

Compound Identifiers

PubChem CID

35028748