Panobinostat (LBH589)

Alias: NVP-LBH589; NVP-LBH 589; LBH589; LBH 589; LBH-589; Panobinostat; Brand name Farydak

Cat No.:V0257 Purity: ≥98%

COA Product Data Instructions for use SDS

Panobinostat (formerlyknown as LBH-589 and NVP LBH-589; trade name Farydak)is a novel, potent and broad-spectrum/non-selective/pan-HDAC inhibitor with potential anticancer activity.

Panobinostat (LBH589) Chemical Structure CAS No.: 404950-80-7
Product category: HDAC

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Panobinostat (LBH589):

Panobinostat lactate

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Panobinostat (formerly known as LBH-589 and NVP LBH-589; trade name Farydak) is a novel, potent and broad-spectrum/non-selective/pan-HDAC inhibitor with potential anticancer activity. It inhibits HDAC in a cell-free assay with an IC50 of 5 nM. It also induces strong cell growth inhibition, cell-cycle arrest, and apoptosis in a time- and dose-dependent manner in both Philadelphia chromosome-negative (Ph-) activate lymphoblastic leukemia (ALL) cell lines. These effects are associated with the induction of histone (H3K9 and H4K8) hyperacetylation, activation of p21 and p27, and suppression of c-Myc. It not only induces apoptosis in multiple myeloma cells through caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage. The FDA approved panobinostat in February 2015 for the treatment of multiple myeloma patients who had undergone at least two prior treatments, such as bortezomib and an immunomodulatory drug.

Biological Activity I Assay Protocols (From Reference)

Targets

HDAC; HIV-1

ln Vitro

LBH589 causes MOLT-4 and Reh cells to undergo apoptosis in a dose- and time-dependent way. LBH589 is also more effective in MOLT-4 cells as opposed to Reh cells. After 48 hours, LBH589 significantly and dose-dependently inhibits the growth of MOLT-4 and Reh cells. Comparing the number of cells in the G2/M phase of the cell cycle with the control cells, LBH589 treatment results in a 2- to 3-fold increase. In addition to lowering c-Myc expression levels in a dose-dependent manner, LBH589 is linked to the induction of histone H3K9 and histone H4K8 acetylation. Additionally, the administration of LBH589 raises p21 expression levels. In Reh cells, LBH589 treatment also reduces c-Myc levels following an initial rise at the lowest dose (10 nM). Furthermore, LBH589 causes significant increases in proapoptosis and DNA repair gene mRNA levels. At the GADD45G promoter, LBH589 increases the amounts of acetylated histone H3 and H4.[1] Furthermore, LBH589 suppresses the growth of mesothelioma (human OK-6 and Ok-5 with IC50 of 5 nM and 7 nM, respectively), small cell lung cancer (human RG-1 and LD-T with IC50 of 4 nM and 5 nM, respectively), and non-small cell lung cancer (human H1299, L55, and A549 with IC50 of 5 nM, 11 nM, and 30 nM, respectively).[2]

ln Vivo

LBH589 significantly reduces tumor growth in animal models of mesothelioma and lung cancer by 62%. Immunocompetent and severely combined immunodeficient mice respond to LBH589 just as well, indicating that LBH589's ability to inhibit tumor growth is not a result of direct immunologic effects. LBH589 was administered intraperitoneally five days a week at a dose of 20 mg/kg, resulting in a 70% reduction in growth on average. LBH589 causes 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 when compared to the corresponding control tumors. LBH589 causes a significant tumor regression in tumors derived from SCLC and RG-1, in contrast to the absence of tumor regression notes in NSCLC and Meso-derived xenografted tumors that are treated under the same circumstances and doses. [2]

Enzyme Assay

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

Cell Assay

The annexin V-FITC apoptosis detection kit is used to stain both untreated and LBH589-treated human Ph- acute lymphoblastic leukemia MOLT-4 (T cells) and Reh (pre-B cells) cells. Me. Flow cytometry is used to calculate the percentage of nonviable and apoptotic cells. Using a CyAn ADP Violet cytometer, a minimum of 5 × 10⁴ cells are obtained. The percentages of apoptosis and cell viability are determined by adding together all annexin V-positive, PI-positive, and annexin V/PI-positive cells.Furthermore, percentages of cell viability are calculated by adding together all annexin V-positive, PI-positive, and annexin V/PI-positive cells.

Animal Protocol

SCID (severe combined immunodeficiency) and adult female C57Bl/6 mice are injected with AE17 and TC-1 cancer cells (1×10⁶ cells) in their flanks. Additional cells are injected into the flanks of SCID mice, but this time with matrigel present: M30 (10×10⁶), A549 (5×10⁶), H69 (2.5×10⁶), BK-T (6.5×10⁶), H526 (10×10⁶), and RG1 (10×10⁶). During the entire experiment, panobinostat is given intraperitoneally (10–20 mg/kg) on a 5-day-on, 2-day-off schedule starting when tumors reach 100–500 mm³. Imperatives of 5% dextrose in water are given intraperitoneally to control mice. Every tumor undergoes at least twice-weekly caliper measurements. Mice with SCID tumors bearing H69 tumors are given panobinostat to assess the impact of combination therapy on SCLC-derived tumors.

References

[1]. Blood . 2008 May 15;111(10):5093-100.

[2]. Mol Cancer Ther . 2009 Aug;8(8):2221-31.

[3]. Haematologica . 2010 May;95(5):794-803.

[4]. Cancer Res . 2006 Jun 1;66(11):5781-9.

[5]. Cancer Lett . 2009 Aug 8;280(2):233-41.

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

Physicochemical Properties

Molecular Formula	C21H23N3O2
Molecular Weight	349.43
Exact Mass	349.18
Elemental Analysis	C, 72.18; H, 6.63; N, 12.03; O, 9.16
CAS #	404950-80-7
Related CAS #	404950-80-7;960055-56-5 (lactate); 960055-60-1 (mesylate);960055-50-9 (acetate); 960055-54-3 (fumarate); 960055-57-6
Appearance	White to off-white solid powder
SMILES	CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)/C=C/C(=O)NO
InChi Key	FPOHNWQLNRZRFC-ZHACJKMWSA-N
InChi Code	InChI=1S/C21H23N3O2/c1-15-18(19-4-2-3-5-20(19)23-15)12-13-22-14-17-8-6-16(7-9-17)10-11-21(25)24-26/h2-11,22-23,26H,12-14H2,1H3,(H,24,25)/b11-10+
Chemical Name	(E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide
Synonyms	NVP-LBH589; NVP-LBH 589; LBH589; LBH 589; LBH-589; Panobinostat; Brand name Farydak
HS Tariff Code	2934.99.9001
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

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: 5mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8618 mL	14.3090 mL	28.6180 mL
	5 mM	0.5724 mL	2.8618 mL	5.7236 mL
	10 mM	0.2862 mL	1.4309 mL	2.8618 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04341311	Active Recruiting	Drug: Panobinostat Drug: Marizomib	Pediatric Cancer Diffuse Glioma	Dana-Farber Cancer Institute	August 10, 2020	Phase 1
NCT02717455	Active Recruiting	Drug: LBH589	Glioma	Pediatric Brain Tumor Consortium	June 28, 2016	Phase 1
NCT02471430	Active Recruiting	Drug: Pegylated Interferon-alpha2a Drug: Panobinostat	HIV Infection	Massachusetts General Hospital	May 2016	Phase 1 Phase 2
NCT02506959	Active Recruiting	Drug: Panobinostat Drug: Melphalan	Plasma Cell Leukemia Plasmacytoma	M.D. Anderson Cancer Center	September 14, 2015	Phase 2
NCT02386800	Recruiting	Drug: panobinostat Drug: ruxolitinib	Thalassemia Polycythemia Vera	Novartis Pharmaceuticals	March 5, 2015	Phase 4

Biological Data

Action of LBH589 on acetylation of histone H4 in myeloma cells and on the proliferation of multiple myeloma cells. Cancer Res . 2006 Jun 1;66(11):5781-9.
LBH589 causes death of patient cells with multiple myeloma and potentiates the antimyeloma action of bortezomib, dexamethasone, and melphalan. Cancer Res . 2006 Jun 1;66(11):5781-9.
Efficacy of the in vitro combinations of panobinostat with other anti-myeloma agents in MM. Haematologica . 2010 May;95(5):794-803.
Efficacy of single-agent panobinostat in xenograft models of MM. Haematologica . 2010 May;95(5):794-803.
LBH589 inhibits proliferation of MOLT-4 and Reh cells. Blood . 2008 May 15;111(10):5093-100.
LBH589 blocks cell-cycle progression of MOLT-4 and Reh cells. Blood . 2008 May 15;111(10):5093-100.
LBH589 induces hyperacetylation of histones H3K9 and H4K8, and modulates expression of cell-cycle control genes. Blood . 2008 May 15;111(10):5093-100.