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    Fangchinoline
    Information
    CAS No. 436-77-1 Price $40 / 20mg
    Catalog No.CFN99167Purity>=98%
    Molecular Weight608.71Type of CompoundAlkaloids
    FormulaC37H40N2O6Physical DescriptionPowder
    Download Manual    COA    MSDSSimilar structuralComparison (Web)
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    Biological Activity
    Description: Fangchinoline is a nonspecific Ca2+ channel blocker, which has neuroprotective, antioxidant, anti-inflammatory, anti-cancer, vasodilating and hypotensive effects. It inhibited cell proliferation via Akt/GSK-3beta/ cyclin D1 signaling and induceed apoptosis in MDA-MB-231 breast cancer cells. It can inhibit human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing.
    Targets: FAK | MMP(e.g.TIMP) | Akt | MEK | ERK | GSK-3 | Bcl-2/Bax | HIV | CDK | p21 | Calcium Channel | MAPK | IL Receptor
    In vitro:
    PLoS One. 2012;7(6):e39225.
    Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing.[Pubmed: 22720080]
    The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs.
    METHODS AND RESULTS:
    In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (Fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 μM. Mechanism-of-action studies showed that Fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of Fangchinoline seems to be HIV-1 envelope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by Fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that Fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions.
    CONCLUSIONS:
    Collectively, our results demonstrate that Fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach.
    Biochem Pharmacol. 2003 Nov 1;66(9):1853-60.
    Fangchinoline inhibits rat aortic vascular smooth muscle cell proliferation and cell cycle progression through inhibition of ERK1/2 activation and c-fos expression.[Pubmed: 14563495]
    Fangchinoline (FAN; a plant alkaloid isolated from Stephania tetrandrae) is a nonspecific Ca(2+) channel blocker. The objective of the present study was to investigate the effect of FAN on the growth factor-induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs).
    METHODS AND RESULTS:
    FAN significantly inhibited both 5% fetal bovine serum (FBS)- and 50ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation, [3H]thymidine incorporation into DNA and phosphorylation of extracellular signal-regulated kinase 1/2. In accordance with these findings, FAN revealed blocking of the FBS-inducible progression through G(0)/G(1) to S phase of the cell cycle in synchronized cells and caused a 62% decrease in the early elevation of c-fos expression induced after 5% FBS addition. Furthermore, significant antiproliferative activity of FAN is observed at concentrations below those required to achieve significant inhibition of Ca(2+) channels by FAN. These results suggest that FAN reduced both FBS- and PDGF-BB-induced RASMCs proliferation by perturbing cell cycle progression.
    CONCLUSIONS:
    This antiproliferative effect of FAN is dependent on the MAP kinase pathway, but cannot be limited to its Ca(2+) modulation.
    J Ethnopharmacol. 2000 Feb;69(2):173-9.
    Anti-inflammatory effects of fangchinoline and tetrandrine.[Pubmed: 10687873]
    Fangchinoline and tetrandrine are the major alkaloids from Stephania tetrandrae S. Moore which has been used traditionally for the treatment of inflammatory diseases in oriental countries including Korea.
    METHODS AND RESULTS:
    Both Fangchinoline and tetrandrine showed anti-inflammatory effects on mouse ear edema induced by croton oil. In addition, the effects of Fangchinoline and tetrandrine on cyclooxygenase, murine interleukin-5 (mIL-5) and human interleukin-6 (hIL-6) were examined in vitro to investigate the anti-inflammatory action mechanisms. One hundred micromolar of Fangchinoline showed 35% of inhibition on cyclooxygenase, but the same concentration of tetrandrine did not show any inhibition. On the other hand, 12.5 microM of tetrandrine exhibited 95% of inhibition on mIL-5 activity, while Fangchinoline did not show any effects. However, 4 microM of Fangchinoline and 6 microM of tetrandrine showed 63 and 86% of inhibitions on hIL-6 activity, respectively.
    CONCLUSIONS:
    These results suggest that biochemical mechanisms of Fangchinoline and tetrandrine on anti-inflammation are significantly different even though they are similar in chemical structure.
    In vivo:
    J Ethnopharmacol. 1997 Oct;58(2):117-23.
    Vasodilating and hypotensive effects of fangchinoline and tetrandrine on the rat aorta and the stroke-prone spontaneously hypertensive rat.[Pubmed: 9406900]
    Comparative studies of the effects of tetrandrine (TET) and Fangchinoline (FAN), two major components of the Radix of Stephannia tetrandrae, on vasodilations and on calcium movement in vascular smooth muscle, and studies of hypotensive effects on stroke-prone spontaneously hypertensive rats (SHRSP) were performed in the following experiments.
    METHODS AND RESULTS:
    TET and FAN inhibited high K+ (65.4 mM) and induced sustained contraction in the rat aorta smooth muscle strips. IC50 values for TET and FAN were 0.27 +/- 0.05 microM (n = 6) and 9.53 +/- 1.57 microM (n = 6), respectively, and this inhibition was antagonized by increasing the Ca2+ concentration in the medium. The IC50 of TET for norepinephrine (NE)-induced contraction (0.86 +/- 0.04 g) was 3.08 +/- 0.05 microM (n = 4), and the IC50 of FAN for NE-induced contraction (0.88 +/- 0.07 g) was 14.20 +/- 0.40 microM (n = 4). At the molecular level, radiolabelled 45Ca2+ uptake tests revealed that TET and FAN also inhibited high K+ (65.4 mM) and 1 microM NE-stimulated Ca2+ influx in rat aorta strips at the maximal concentration was needed to inhibit the contraction. TET (3 mg/kg) and FAN (30 mg/kg) administered by intravenous (i.v.) bolus injection also lowered the mean arterial pressure (MAP) significantly during the period of observation in conscious SHRSP, respectively.
    CONCLUSIONS:
    These results showed that TET was more potent than FAN in blocking calcium channels and antihypertensive activity.
    Fangchinoline Description
    Source: The vines of Cocculus orbiculatus (L.) DC.
    Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
    Storage: Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).

    Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.

    Need more advice on solubility, usage and handling? Please email to: service@chemfaces.com

    After receiving: The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
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    Calculate Dilution Ratios(Only for Reference)
    1 mg 5 mg 10 mg 20 mg 25 mg
    1 mM 1.6428 mL 8.2141 mL 16.4282 mL 32.8564 mL 41.0705 mL
    5 mM 0.3286 mL 1.6428 mL 3.2856 mL 6.5713 mL 8.2141 mL
    10 mM 0.1643 mL 0.8214 mL 1.6428 mL 3.2856 mL 4.107 mL
    50 mM 0.0329 mL 0.1643 mL 0.3286 mL 0.6571 mL 0.8214 mL
    100 mM 0.0164 mL 0.0821 mL 0.1643 mL 0.3286 mL 0.4107 mL
    * Note: If you are in the process of experiment, it's need to make the dilution ratios of the samples. The dilution data of the sheet for your reference. Normally, it's can get a better solubility within lower of Concentrations.
    Protocol
    Cell Research:
    J Drug Target. 2015 Apr;23(3):266-74.
    Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway in A549.[Pubmed: 25539072]
    Fangchinoline as a novel anti-tumor agent has been paid attention in several types of cancers cells except lung cancer. Here we have investigated the effect of Fangchinoline on A549 cells and its underlying mechanism. The purpose of this work was to study the effect of Fangchinoline on A549 cells.
    METHODS AND RESULTS:
    Four lung cancer cell lines (A549, NCI-H292, NCI-H446, and NCI-H460) were exposed to varying concentrations (10-40 μmol/l) of Fangchinoline to observe the effect of Fangchinoline on the four lung cancer cell lines and to observe the changes of the lung cancer cell on proliferation, apoptosis, and invasion. Fangchinoline effectively suppressed proliferation and invasion of A549 cell line but not NCI-H292, NCI-H446, and NCI-H460 cell lines by inhibiting the phosphorylation of FAK (Tyr397) and its downstream pathways, due to the significant differences of Fak expression between A549 and the other three cell lines. And all FAK-paxillin/MMP2/MMP9 pathway, FAK-Akt pathway, and FAK-MEK-ERK1/2 pathway could be inhibited by Fangchinoline. Fangchinoline effectively suppressed proliferation and invasion of A549 cell line by inhibiting the phosphorylation of FAK (Tyr397) and its downstream pathways.
    CONCLUSIONS:
    Fangchinoline could inhibit the phosphorylation of FAK(p-Tyr397), at least partially. Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway and inhibits the growth and the invasion in tumor cells which highly expressed FAK such as A549 cell line.
    Asian Pac J Cancer Prev. 2014;15(2):769-73.
    Fangchinoline inhibits cell proliferation via Akt/GSK-3beta/ cyclin D1 signaling and induces apoptosis in MDA-MB-231 breast cancer cells.[Pubmed: 24568493]
    Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated.
    METHODS AND RESULTS:
    Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk- 3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA- MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis.
    CONCLUSIONS:
    Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.