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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LoVoMUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NX7K[lZmPzJiaB?=NFT3bG1FVVORMXLJR|UxRTVwMfMAjeKy6oDLMD62JI5OM3PL[VI{Ojl7M{i4
RKOMVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mk\YO|IhcA>?M3j4S2ROW09?M4O0RmlEPTB;Nz655qCKyrIkgJmyMlIhdk1?M{[zdlI{Ojl7M{i4
SW480NVPrTXNST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NU\pfpNSPzJiaB?=M3POeWROW09?MUXJR|UxRTF5LkZihKnDueLCiUCuPEBvVQ>?NGX4NYEzOzJ7OUO4PC=>
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... 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 2016-07-30)

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
2 years -80℃in solvent
Synonyms NVP-LBH589
Solubility (25°C) * In vitro DMSO 69 mg/mL (197.46 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 2% DMSO+48% PEG 300+2% Tween 80+ddH2O 5mg/mL
* <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

Frequently Asked Questions

  • Question 1
    How to reconstitute the compound for in vivo mice study?

    Answer: We recommend the vehicle is 2 % DMSO, 2 % Tween 80, 48%PEG300, 48% water. The compound is first dissolved in DMSO, then add Tween, PEG300, water in sequence.

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

If you have any other enquiries, please leave a message.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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