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LW6

Catalog No. T3494   CAS 934593-90-5
Synonyms: LW 6, Apoptosis, LW-8, Hypoxia-inducible factors, inhibit, HIF-PH, HIF/HIF Prolyl-Hydroxylase, HIF-1α inhibitor, LW8, LW6, CAY10585, LW-6, HIFs, Inhibitor, LW 8

LW6 is a novel HIF-1 inhibitor.

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LW6, CAS 934593-90-5
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Purity: 98%
Biological Description
Chemical Properties
Storage & Solubility Information
Description LW6 is a novel HIF-1 inhibitor.
Targets&IC50 MDH2:6.3 μM, HIF:4.4 μM
In vitro LW6 decreases the expression of HIF-1α protein without affecting HIF-1β expression. LW6 affects the stability of the HIF-1α protein. LW6 promotes 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 induces 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 expression[2]. 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[3]. LW6 inhibits the expression of HIF 1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel Lindau protein. LW6 induces hypoxia selective apoptosis together with a reduction in the mitochondrial membrane potential[4].
In vivo LW6 demonstrates strong anti-tumor efficacy in vivo and causes a decrease in HIF-1α expression in frozen-tissue immunohistochemical staining in mice carrying xenografts of human colon cancer HCT116 cells[2].
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 luminometer[2].
Synonyms LW 6, Apoptosis, LW-8, Hypoxia-inducible factors, inhibit, HIF-PH, HIF/HIF Prolyl-Hydroxylase, HIF-1α inhibitor, LW8, LW6, CAY10585, LW-6, HIFs, Inhibitor, LW 8
Molecular Weight 435.52
Formula C26H29NO5
CAS No. 934593-90-5

Storage

Powder: -20°C for 3 years

In solvent: -80°C for 2 years

Solubility Information

DMSO: 33 mg/mL

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Citations

References and Literature
1. Zhu B, Wu Y, Huang S, et al. Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection. Immunity. 2021, 54(6): 1200-1218. e9. 1. Naik R , Won M , Ban H S , et al. Synthesis and Structure–Activity Relationship Study of Chemical Probes as Hypoxia Induced Factor-1α/Malate Dehydrogenase 2 Inhibitors[J]. Journal of Medicinal Chemistry, 2014, 57(22):9522-9538. 2. Lee K, et al. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010 Oct 1;80(7):982-9. 3. Song JG, et al. Discovery of LW6 as a new potent inhibitor of breast cancer resistance protein. 4. Sato M, et al. LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep. 2015 Sep;12(3):3462-8. 5. Zhu B, Wu Y, Huang S, et al. Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection[J]. Immunity. 2021

Related compound libraries

This product is contained In the following compound libraries:
Anti-Cancer Compound Library HIF-1 Signaling Pathway Compound Library Glycometabolism Compound Library Anti-Cancer Metabolism Compound Library Glutamine Metabolism Compound Library Anti-Pancreatic Cancer Compound Library Inhibitor Library Anti-Metabolism Disease Compound Library Stem Cell Differentiation Compound Library Apoptosis Compound Library

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