LW 6

Catalog No.S8441

LW 6 Chemical Structure

Molecular Weight(MW): 435.51

LW6 is a hypoxia-inducible factor 1(HIF) inhibitor which potently inhibits HIF-1α accumulation by degrading HIF-1α without affecting the HIF-1a mRNA levels during hypoxia. It inhibits hypoxia-induced HIF-1α transcription activity with IC50 of 2.64 μM in cell-based HRE-reporter gene assays.

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Biological Activity

Description LW6 is a hypoxia-inducible factor 1(HIF) inhibitor which potently inhibits HIF-1α accumulation by degrading HIF-1α without affecting the HIF-1a mRNA levels during hypoxia. It inhibits hypoxia-induced HIF-1α transcription activity with IC50 of 2.64 μM in cell-based HRE-reporter gene assays.
In vitro

LW6 inhibits HIF-1α expression induced by hypoxia. It promotes apoptosis preferentially in hypoxic cells. Treatment with LW6 presents no additive effect on cell cycle arrest. LW6 induces ROS formation through the depolarization of MMP in hypoxic cells. Although LW6 increases mitochondrial ROS production, the combination with hypoxia induces a marked increase in ROS production and this high level is maintained up until 24 h. LW6 is also a specific inhibitor of MDH2. As MDH2 is known to serve a significant role in the citric acid cycle at the mitochondrial membrane, LW6 indirectly reduces the activity of the mitochondrial respiratory chain through the inhibition of MDH2[1]. In MDCKII-BCRP cells overexpressing BCRP, LW6 enhances significantly (p < 0.05) the cellular accumulation of mitoxantrone, a BCRP substrate, and is more potent than Ko143, a well-known BCRP inhibitor. In contrast to BCRP, LW6 has no inhibition effect on the functional activity and gene expression of P-gp[2]. LW6 also down-regulates BCRP expression at concentrations of 0.1-10 μM. Furthermore, cells become more susceptible to the cytotoxicity of anticancer drugs in the presence of LW6[3].

In vivo LW6 exerts marked anti-tumor efficacy in vivo and causes reductions in HIF-1α expression levels in mice carrying xeno-grafts of HCT116 cells[1]. LW6 improves the cytotoxicity and bioavailability of anticancer drugs translocated by BCRP[3].

Protocol

Cell Research:

[1]

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  • Cell lines: A549 cells
  • Concentrations: 5-100 μM
  • Incubation Time: 24 h
  • Method:

    Cells are incubated in 96-well ELISA Plates with 100 μl culture medium at 2×105 cells/ml with or without LW6 for 24 h. Cell viability is assessed by the dimethyl thiazolcarboxy-methoxyphenylsulfophenyltetrazolium (MTS) assay. The absorbance is measured at 490 and 620 nm using a microplate reader. For the trypan blue dye. exclusion test, cells are stained by phosphate-buffered saline (PBS) containing 0.1% trypan blue. Cell viability is assessed by counting the number of unstained cells.


    (Only for Reference)
Animal Research:

[3]

+ Expand
  • Animal Models: Male Sprague-Dawley rats
  • Formulation: 20% DMA/45% HP-β-CD in water
  • Dosages: 10 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 13 mg/mL (29.85 mM)
Ethanol 1 mg/mL (2.29 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 435.51
Formula

C26H29NO5

CAS No. 934593-90-5
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID