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    Panobinostat (LBH589)
    Panobinostat (LBH589)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0257
    CAS #: 404950-80-7Purity ≥98%

    Description: Panobinostat (formerly known as LBH589 and NVP LBH-589; trade name Farydak) is a novel, potent and broad-spectrum/non selective HDAC inhibitor with IC50 of 5 nM in a cell-free assay. It not only induces apoptosis in multiple myeloma cells via caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage, but also induces potent cell growth inhibition, cell-cycle arrest, and apoptosis in a time- and dose-dependent manner in both Philadelphia chromosome-negative (Ph-) actue lymphoblastic leukemia (ALL) cells lines, which are correlated with induction of histone (H3K9 and H4K8) hyperacetylation, activation of p21 and p27, and suppression of c-Myc. In February 2015, Panobinostat received FDA approval for treating patients with multiple myeloma who had received at least 2 previous treatments, including bortezomib and an immunomodulatory agent.

    References: Blood. 2008 May 15;111(10):5093-100; Mol Cancer Ther. 2009 Aug;8(8):2221-31; Cancer Res. 2006 Jun 1;66(11):5781-9.

    Related CAS #: 404950-80-7 (free base); 960055-56-5 (lactate); 960055-60-1 (mesylate); 960055-50-9 (acetate); 960055-54-3 (fumarate); 960055-57-6 (maleate)    

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    Molecular Weight (MW)349.43
    FormulaC21H23N3O2
    CAS No.404950-80-7
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 69 mg/mL (197.5 mM)
    Water: <1 mg/mL
    Ethanol:  <1 mg/mL
    Solubility (In vivo)2% DMSO+48% PEG 300+2% Tween 80+ddH2O: 5 mg/mL
    SynonymsNVP-LBH589; NVP-LBH 589; LBH589; LBH 589; LBH-589; Panobinostat; Brand name Farydak


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    In Vitro

    In vitro activity: LBH589 induces apoptosis among MOLT-4 and Reh cells in a time- and dose-dependent manner. Moreover, LBH589 is more potent in MOLT-4 than in Reh cells. LBH589 markedly prevents the growth of both MOLT-4 and Reh cells in a dose-dependent manner at 48 hours. LBH589 treatment causes a 2- to 3-fold increase in the number of cells in the G2/M phase of the cell cycle compared with the control cells. LBH589 is associated with induction of histone H3K9 and histone H4K8 acetylation as well as decreasing levels of c-Myc expression in a dose-dependent manner. LBH589 treatment also increases the levels of p21 expression. LBH589 treatment also decreases the levels of c-Myc after an initial increase at the lowest dose (10 nM) in Reh cells. In addition, LBH589 gives rise to substantial increases in mRNA levels of proapoptosis and DNA repair genes. LBH589 induces increased levels of acetylated histone H3 and H4 at the GADD45G promoter. Besides, LBH589 inhibits growth of non small cell lung cancer cell lines (such as human H1299, L55 and A549 with IC50 of 5 nM, 11 nM and 30 nM, respectively), mesothelioma (such as human OK-6 and Ok-5 with IC50 of 5 nM and 7 nM, respectively) and small cell lung cancer cell lines (such as human RG-1 and LD-T with IC50 of 4 nM and 5 nM, respectively).


    Kinase Assay: Panobinostat is a non-selective histone deacetylase (HDAC) inhibitor.


    Cell Assay:  Untreated and LBH589-treated cells [human Ph- acute lymphoblastic leukemia MOLT-4 (T cells) and Reh (pre-B cells)] are stained with annexin V and propidium iodide using annexin V-FITC apoptosis detection kit I. The percentage of apoptotic and nonviable cells is determined by flow cytometry. At least 5 × 104 cells are collected with a CyAn ADP Violet cytometer. Percentage apoptosis is calculated considering all the annexin V-positive plus the annexin V/PI-positive cells; percentage loss of cell viability is calculated considering all the annexin V-positive plus the PI-positive and the annexinV/PI-positive cells.

    In VivoIn lung cancer and mesothelioma animal models, LBH589 markedly decreases tumor growth by 62%. LBH589 is equally effective in immunocompetent and severe combined immunodeficien-cymice, suggesting that the inhibition of tumor growth by LBH589 is not due to direct immunologic effects. Daily LBH589, given i.p. at 20 mg/kg for 5 days per week, leading to an average decrease in growth of 70%. Compared with the corresponding control tumors, LBH589 leads to a 53% decrease for H526-derived tumors, an 81% decrease for BK-T-derived tumors, a 76% decrease for RG-1- derived tumors, and a 70% decrease for H69-derived tumors. In contrast to the lack of tumor regression notes in NSCLC and Meso-derived xenografted tumors that are treated under identical conditions and doses, LBH589 results in dramatic tumor regression in SCLC-derived tumors and RG-1-derived tumor.
    Animal modelSevere combined immunodeficiency (SCID) mice with M30 (107 cells) or A549 (5 × 106 cells), H69 (2.5 × 106 cells), BK-T (6.5 × 106), H526 (10 × 106), and RG1 (10 × 106) cells
    Formulation & DosageDissolved in Dextrose 5% in water; 10 mg/kg, 20 mg/kg; i.p. injections
    ReferencesBlood. 2008 May 15;111(10):5093-100; Mol Cancer Ther. 2009 Aug;8(8):2221-31; Cancer Res. 2006 Jun 1;66(11):5781-9.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

     

    Panobinostat (LBH589)

     

    Panobinostat (LBH589)

     

    Panobinostat (LBH589)


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