Panobinostat (LBH589)

Catalog No.S1030

Panobinostat (LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Phase 3.

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Panobinostat (LBH589) Chemical Structure

Panobinostat (LBH589) Chemical Structure
Molecular Weight: 349.43

Validation & Quality Control

Cited by 44 publications:

8 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Panobinostat (LBH589) is available in the following compound libraries:

HDAC Inhibitors with Unique Features

Product Information

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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Panobinostat (LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Phase 3.
Targets HDAC (MOLT-4 cells) [1] HDAC (Reh cells) [1]
IC50 5 nM 20 nM
In vitro 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. [1] 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). [2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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dHCT116 p21−/−NGG0eFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXXXc45FPzJiaB?=M{Cyc2ROW09?M2G4Z2lEPTB;NT655qCKyrIkgJmxMlMhdk1?NHrOeoYzOzJ7OUO4PC=>
HT29M2m3W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFHqVG04OiCqNETzZ3FFVVORNVe3cmVTUUN3ME2xOk4{6oDLwsJihKkzNjNibl2=NGTpVXYzOzJ7OUO4PC=>
LoVoM3fHVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mmj6O|IhcA>?M3e3NWROW09?M1T5O2lEPTB;NT6x5qCKyrIkgJmwMlYhdk1?MX6yN|I6QTN6OB?=
RKOMUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mlj6O|IhcA>?MkC3SG1UVw>?NULBNYVQUUN3ME23MlnjiIoEsfMAjVIvOiCwTR?=MoLENlMzQTl|OEi=
SW480MlTXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGC0PXo4OiCqNEP0bHFFVVORNUW2VWxrUUN3ME2xO{426oDLwsJihKkxNjhibl2=NHjOelEzOzJ7OUO4PC=>
eSW620NYDUXYk3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MUi3NkBpNGrRdpZFVVORM3LsZ2lEPTB;OT6x5qCKyrIkgJmyMlEhdk1?MnrTNlMzQTl|OEi=

... Click to View More Cell Line Experimental Data

In vivo In 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. [2]
Features

Protocol(Only for Reference)

Cell Assay: [1]

Cell lines MOLT-4 cell lines and Reh (pre-B cells)
Concentrations 50 nM
Incubation Time 48 hours
Method 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.

Animal Study: [2]

Animal Models Severe 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 Dextrose 5% in water
Dosages 10 mg/kg, 20 mg/kg
Administration Administered via i.p. injection

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Scuto A, et al. Blood. 2008, 111(10), 5093-5100.

[2] Crisanti MC, et al. Mol Cancer Ther. 2009, 8(8), 2221-2231.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-06-25)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02802163 Not yet recruiting Multiple Myeloma H. Lee Moffitt Cancer Center and Research Institute|Novar  ...more H. Lee Moffitt Cancer Center and Research Institute|Novartis|Amgen September 2016 Phase 1|Phase 2
NCT02756663 Not yet recruiting Multiple Myeloma Novartis Pharmaceuticals|Novartis June 2016 Phase 2
NCT02722941 Recruiting Multiple Myeloma H. Lee Moffitt Cancer Center and Research Institute|Novar  ...more H. Lee Moffitt Cancer Center and Research Institute|Novartis Pharmaceuticals June 2016 Phase 2
NCT02471430 Recruiting HIV Infection Massachusetts General Hospital|Novartis|Genentech, Inc. May 2016 Phase 1|Phase 2
NCT02654990 Recruiting Multiple Myeloma Novartis Pharmaceuticals|Novartis April 2016 Phase 2

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Chemical Information

Download Panobinostat (LBH589) SDF
Molecular Weight (MW) 349.43
Formula

C21H23N3O2

CAS No. 404950-80-7
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms NVP-LBH589
Solubility (25°C) * In vitro DMSO 69 mg/mL (197.46 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 2% DMSO, 2% Tween 80, 48% PEG 300 5
* <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.
Chemical Name (E)-N-hydroxy-3-(4-((2-(2-methyl-1H-indol-3-yl)ethylamino)methyl)phenyl)acrylamide

Customer Product Validation(8)


Click to enlarge
Rating
Source Breast Cancer Res Treat 2012 131, 777-789. Panobinostat (LBH589) purchased from Selleck
Method MTT growth inhibition and Drug combination index (CI) analysis
Cell Lines MDA-MB-231 cells
Concentrations
Incubation Time 48 h
Results At very low dose combination (fractional growth inhibition, Fa= 0.9), synergistic growth inhibition (CI<1) was observed between pargyline and HDAC inhibitors SAHA, TSA, MS-275, and LBH-589.At median or higher dose combination (Fa= 0.5 or 0.75), pargyline exhibited synergy with all the HDAC inhibitors tested (CI<1).

Click to enlarge
Rating
Source PLoS One 2011 6, e17138. Panobinostat (LBH589) purchased from Selleck
Method Western blot, Enzymatic Assays, Assessment of Baseline and Drug Induced Apoptosis
Cell Lines THP-1 cells
Concentrations 0.7 μM
Incubation Time 3 h/24 h
Results Treatments with LBH-589, PXD101, and SAHA, but not with the other HDACIs, resulted in hyperacetylation of a-tubulin, the substrate of HDAC6 (Figure A). IP followed by enzymatic assays revealed that both LBH-589 and PXD101 treatments resulted in the greatest inhibition of HDAC1 activities (>80% relative to control), compared to other HDACIs tested (Figure C). This was accompanied by significantly higher extents of proliferation inhibition (as reflected in percent decrease of live cells relative to untreated cells) and apoptosis (Figures E&F). Essentially the same results were obtained in THP-1 cells when the HDACI treatments were extended to 24 h, though the levels of apoptosis induced by the drugs were substantially higher (Figures B, D, E&F).

Click to enlarge
Rating
Source PLoS One 2011 6, e17138. Panobinostat (LBH589) purchased from Selleck
Method Western blot
Cell Lines THP-1 cells
Concentrations 0.7 μM
Incubation Time 3 h/24 h
Results Effects of LBH589 and other HDACIs on p21, c-Myc, and Bim expression, and in inducing DNA damage (as reflected in cH2AX) were both drug-dependent and time-dependent, as reflected in results at 3h and 24h.

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Rating
Source PLoS One 2011 6, e20920. Panobinostat (LBH589) purchased from Selleck
Method Cell Survival Assays
Cell Lines MTDH knockdown Hec50co cells
Concentrations 10-40 nM
Incubation Time 72 h
Results Compared with scrambled shRNA transfected Hec50co cells, stable MTDH knockdown modestly increased the sensitivity of Hec50co cells to LBH589.

Click to enlarge
Rating
Source PLoS One 2011 6, e20920. Panobinostat (LBH589) purchased from Selleck
Method Western blot
Cell Lines MTDH knockdown Hec50co cells
Concentrations 20 nM
Incubation Time 24 h
Results Expression of proteins associated with apoptosis(both pro- and anti-apoptotic factors) were tested in MTDH control and knockdown cells after single treatment (LBH589 or TRAIL) or after combined treatment (LBH589 and TRAIL). The combination treatment did not enhance expression of the TRAIL receptors DR4 and DR5. Additionally, there were no changes in expression of anti-apoptotic genes Bcl-xL, Mcl-1, or FLIP in MTDH control and knockdown Hec50co cells after the combinatorial treatment.

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Rating
Source Biochem Bioph Res Co 2009 391, 1748-1751. Panobinostat (LBH589) purchased from Selleck
Method Western blot
Cell Lines p53(+/+) cells, (-/-)HCT116 cells
Concentrations 2–5 μM
Incubation Time 24 h
Results while TAp63 protein was up-regulated efficiently by LBH589, TSA, and MS-275 in HCT116 cells, these agents failed to induce p63 expression in the p53 null counterparts.

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Rating
Source Dr.Zhang of Tianjin Medical University. Panobinostat (LBH589) purchased from Selleck
Method Western blot
Cell Lines
Concentrations 0-10 μM
Incubation Time
Results

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Rating
Source Dr. Berna S. Sayan of Leicester University. Panobinostat (LBH589) purchased from Selleck
Method Western blot
Cell Lines HCT116 cells
Concentrations 10 μM
Incubation Time 24 h
Results

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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