LW6 (HIF-1α inhibitor) (Synonyms: Hypoxia-Inducible Factor1α Inhibitor) |
| Katalog-Nr.GC32724 |
LW6 (HIF-1α-Inhibitor) ist ein neuartiger HIF-1-Inhibitor mit einer IC50 von 4,4 μM. LW6 (HIF-1α-Inhibitor) reduziert die Proteinexpression von HIF-1α, ohne die Expression von HIF-1β zu beeinflussen.
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Cas No.: 934593-90-5
Sample solution is provided at 25 µL, 10mM.
LW6 is a hypoxia-inducing factor 1(HIF) inhibitor, which effectively inhibits HIF-1α accumulation by degrading HIF-1α, but does not affect HIF-1A mRNA level during hypoxia. LW6 inhibits the expression of HIF and MDH2, with IC50 values of 4.4 and 6.3µM, respectively [1-2].
LW6(0.01-25µM ; 30 min) enhanced significantly the cellular accumulation of mitoxantrone(BCRP substrate)in MDCKII-BCRP cells (overexpressed BCRP)[3]. LW6 inhibited hypoxia-induced HIF1α expression at 20 mM in A549 cells, and at this concentration,LW6 induced hypoxia-selective apoptosis and decreased mitochondrial membrane potential[4]. LW6(40-160µM) inhibited proliferation and induced cell death in a dose-dependent manner In 6606PDA and MIA PaCa-2 cells[5]. LW6 (80µM)significantly inhibited migration,besides,LW6 reduced cell proliferation and induced cell death in a dose dependent manner[6]. LW6(30 µµ; 72 h) stimulates T cells to decrease HIF-1α levels[7]. LW6 inhibited T-cell clonal expansion in two-way mixed lymphocyte reaction (MLR) [8].
LW6(5 mg/kg;i.v/p.o) exhibited a small volume of distribution and a short terminal half-life. LW6 was slowly degraded in mouse liver microsomes and serum. About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively[1].
References:
[1]. Lee K, Lee JH, et,al. (Aryloxyacetylamino)benzoic acid analogues: A new class of hypoxia-inducible factor-1 inhibitors. J Med Chem. 2007 Apr 5;50(7):1675-84. doi: 10.1021/jm0610292. Epub 2007 Mar 1. PMID: 17328532.
[2]. Naik R, Won M, et,al.Synthesis and structure-activity relationship study of chemical probes as hypoxia induced factor-1α/malate dehydrogenase 2 inhibitors. J Med Chem. 2014 Nov 26;57(22):9522-38. doi: 10.1021/jm501241g. Epub 2014 Nov 12. PMID: 25356789.
[3]. Song JG, Lee YS, et,al. Discovery of LW6 as a new potent inhibitor of breast cancer resistance protein. Cancer Chemother Pharmacol. 2016 Oct;78(4):735-44. doi: 10.1007/s00280-016-3127-2. Epub 2016 Aug 12. PMID: 27520631.
[4]. Sato M, Hirose K, 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):3462-3468. doi: 10.3892/mmr.2015.3862. Epub 2015 May 27. PMID: 26017562; PMCID: PMC4526100.
[5]. Zhang X, Kumstel S, et,al. LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer. J Adv Res. 2019 Apr 24;20:9-21. doi: 10.1016/j.jare.2019.04.006. PMID: 31193017; PMCID: PMC6514270.
[6]. Zhang X, Liu P, et,al.Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1. J Cancer. 2020 Jan 1;11(2):479-487. doi: 10.7150/jca.33029. PMID: 31897243; PMCID: PMC6930432.
[7]. Eleftheriadis T, Pissas G, et,al. Malate dehydrogenase-2 inhibitor LW6 promotes metabolic adaptations and reduces proliferation and apoptosis in activated human T-cells. Exp Ther Med. 2015 Nov;10(5):1959-1966. doi: 10.3892/etm.2015.2763. Epub 2015 Sep 22. PMID: 26640580; PMCID: PMC4665222.
[8]. Eleftheriadis T, Pissas G, et,al.Comparison of the effect of the aerobic glycolysis inhibitor dichloroacetate and of the Krebs cycle inhibitor LW6 on cellular and humoral alloimmunity. Biomed Rep. 2017 Nov;7(5):439-444. doi: 10.3892/br.2017.980. Epub 2017 Sep 11. PMID: 29181155; PMCID: PMC5700391.
| Cell experiment [1]: | |
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Cell lines |
MDCKII-BCRP cells (overexpressing BCRP) |
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Preparation Method |
Cells were seeded into a 96-well plate. At 3 days post-seeding, cells were incubated with mitoxantrone (5µM) with/without inhibitor LW6 over the concentration range of 0.01-25µM. After incubation for 30 min, the drug solution was removed and the cells were washed twice with ice-cold PBS. |
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Reaction Conditions |
0.01-25µM; 30 min |
|
Applications |
LW6 enhanced significantly the cellular accumulation of mitoxantrone(BCRP substrate). |
| Animal experiment [2]: | |
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Animal models |
Male ICR mice |
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Preparation Method |
Mice were given a single intravenous (i.v.;5 mg/kg) or oral dose (p.o.;5 mg/kg) of LW6. |
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Dosage form |
5 mg/kg;i.v/p.o; |
|
Applications |
LW6 exhibited a small volume of distribution (0.5 ±0.1 L/kg), and a short terminal half-life (0.6±0.1 h). LW6 was slowly degraded in mouse liver microsomes (t1/2 > 1 h) and serum (t1/2 > 6 h). About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively. |
|
References: [1]. Song JG, Lee YS, et,al.Discovery of LW6 as a new potent inhibitor of breast cancer resistance protein. Cancer Chemother Pharmacol. 2016 Oct;78(4):735-44. doi: 10.1007/s00280-016-3127-2. Epub 2016 Aug 12. PMID: 27520631. |
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| Cas No. | 934593-90-5 | SDF | |
| Überlieferungen | Hypoxia-Inducible Factor1α Inhibitor | ||
| Canonical SMILES | O=C(OC)C1=CC=C(O)C(NC(COC2=CC=C(C3(C4)CC5CC4CC(C5)C3)C=C2)=O)=C1 | ||
| Formula | C26H29NO5 | M.Wt | 435.51 |
| Löslichkeit | DMSO : ≥ 33 mg/mL (75.77 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2962 mL | 11.4808 mL | 22.9616 mL |
| 5 mM | 0.4592 mL | 2.2962 mL | 4.5923 mL |
| 10 mM | 0.2296 mL | 1.1481 mL | 2.2962 mL |
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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