CAY10585 (LW 6)

Catalog No.S8441 Batch:S844101

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Technical Data

Formula

C26H29NO5
Molecular Weight 435.51 CAS No. 934593-90-5
Solubility (25°C)* In vitro DMSO 13 mg/mL (29.85 mM)
Ethanol 1 mg/mL (2.29 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description CAY10585 (LW 6) 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. LW6 inhibits HIF and MDH2 expression with IC50 values of 4.4 and 6.3 μM, respectively.
Targets
BCRP [3] HIF [2]
(Cell-free assay)		 MDH2 [2]
(Cell-free assay)
4.4 μM 6.3 μM
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 (from reference)

Cell Assay:

[1]
  • 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.
Animal Study:

[3]
  • Animal Models

    Male Sprague-Dawley rats

  • Dosages

    10 mg/kg

  • Administration

    p.o.

Selleck's CAY10585 (LW 6) has been cited by 12 publications

WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy [ J Transl Med, 2024, 22(1):245] PubMed: 38448948
Commensal microbiome promotes hair follicle regeneration by inducing keratinocyte HIF-1α signaling and glutamine metabolism [ Sci Adv, 2023, 9(1):eabo7555] PubMed: 36598999
IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways [ Front Immunol, 2022, 13:888719] PubMed: 35757697
Downregulation of miR-491-5p promotes neovascularization after traumatic brain injury [ Neural Regen Res, 2022, 17(3):577-586] PubMed: 34380897
Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo [ Front Pharmacol, 2022, 13:974216] PubMed: 36210813
The PER1/HIF-1alpha negative feedback loop promotes ferroptosis and inhibits tumor progression in oral squamous cell carcinoma [ Transl Oncol, 2022, 18:101360] PubMed: 35134674
Differentiated embryo chondrocyte 1, induced by hypoxia-inducible factor 1α, promotes cell migration in oral squamous cell carcinoma cell lines [ Oral Surg Oral Med Oral Pathol Oral Radiol, 2022, 133(2):199-206] PubMed: 34758939
RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells [ Bioengineered, 2021, 10.1080/21655979.2021.2002499] PubMed: 34752201
FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice [ Ann Rheum Dis, 2020, 79(1):112-122] PubMed: 31662319
MicroRNA-137 exerts protective effects on hypoxia-induced cell injury by inhibiting autophagy/mitophagy and maintaining mitochondrial function in breast cancer stem-like cells [ Oncol Rep, 2020, 44(4):1627-1637] PubMed: 32945512

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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