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Panobinostat (LBH589)

LBH589 (Panobinostat) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM and 20 nM in MOLT-4 and Reh cells, respectively.

Catalog No.S1030

9 Reviews 10 Product Citations

: Tel: +1-832-582-8158[email protected]

Panobinostat (LBH589) Chemical Structure
Molecular Weight: 349.43

Validation & Quality Control

Product Citations(10)

Nat Biotechnol, 2011, 29(3), 255-265

Blood, 2012, 119(6):1450-8

Acta Neuropathol, 2011, 122(5):637-50

Clin Cancer Res, 2012, 18(2), 408-416

Sci Signal, 2010, 3(146), ra80
Breast Cancer Res Treat, 2012, 131(3), 777-789

PloS ONE, 2011, 6(6), e20920

PLoS One, 2011, 6(2), e17138

Cancer Lett, 2013, 329(1):17-26

Biochem Bioph Res Co, 2010, 391(4), 1748-1751

Customer Reviews(9) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

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

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Epigenetics Compound Library (96-well) Inhibitor Library (96-well)

Product Information

Compare HDAC Inhibitors

Research Area
Research Area

Cat.No.	Product Name	Solubility (25°C)
S1053	Entinostat (MS-275, SNDX-275)	<1 mg/mL	75 mg/mL	<1 mg/mL
S1047	Vorinostat (SAHA)	<1 mg/mL	53 mg/mL	3 mg/mL
S1030	Panobinostat (LBH589)	<1 mg/mL	70 mg/mL	<1 mg/mL
S3020	Romidepsin (FK228 ,depsipeptide)	<1 mg/mL	10 mg/mL	<1 mg/mL
S1045	Trichostatin A (TSA)	<1 mg/mL	23 mg/mL	<1 mg/mL
S1122	Mocetinostat (MGCD0103)	<1 mg/mL	13 mg/mL	<1 mg/mL
S2627	Tubastatin A HCl	<1 mg/mL	74 mg/mL	<1 mg/mL
S1085	Belinostat (PXD101)	<1 mg/mL	64 mg/mL	<1 mg/mL
S2170	ITF2357 (Givinostat)	<1 mg/mL	95 mg/mL	3 mg/mL
S1095	LAQ824 (NVP-LAQ824, Dacinostat)	<1 mg/mL	76 mg/mL	<1 mg/mL
S1194	CUDC-101	<1 mg/mL	20 mg/mL	<1 mg/mL
S1515	SB939 (Pracinostat)	<1 mg/mL	72 mg/mL	27 mg/mL
S2012	PCI-34051	<1 mg/mL	59 mg/mL	<1 mg/mL
S1422	Droxinostat	<1 mg/mL	49 mg/mL	49 mg/mL
S1484	MC1568	<1 mg/mL	13 mg/mL	<1 mg/mL
S1090	PCI-24781	<1 mg/mL	80 mg/mL	<1 mg/mL
S1096	JNJ-26481585	<1 mg/mL	79 mg/mL	<1 mg/mL
S1168	Valproic acid sodium salt (Sodium valproate)	33 mg/mL	33 mg/mL	33 mg/mL
S2818	CI994 (Tacedinaline)	<1 mg/mL	≥54 mg/mL	<1 mg/mL
S2244	AR-42 (HDAC-42)	<1 mg/mL	63 mg/mL	63 mg/mL
S2779	M344	<1 mg/mL	62 mg/mL	4 mg/mL
S2759	PI3K/HDAC InhibitorⅠ	<1 mg/mL	102 mg/mL	<1 mg/mL
S8001	Rocilinostat (ACY-1215)	<1 mg/mL	87 mg/mL	<1 mg/mL

Combination Therapy

Combination Therapy

Panobinostat (LBH589) + Dexamethasone	When either of the two recently approved agents for relapsed/refractory MM (Bortezomib and Lenalidomide) is added to the combination of LBH-589 plus Dexamethasone in MM1S cells, the efficacy is clearly superior to the respective individual agents or double combinations. LBH-589 plus Lenalidomide displays very synergistic results with combination index (CI) less than 0.1. Although the double combinations of LBH-589 plus either Lenalidomide or Bortezomib are highly effective, the antitumor activity increased even further with triple combinations. ^[3]
Panobinostat (LBH589) + Bortezomib	Combination of LBH589 with _Bortezomib enhances cytotoxicity against patient multiple myeloma cells. ^[4]
Panobinostat (LBH589) + Lenalidomide	When either of the two recently approved agents for relapsed/refractory MM (Bortezomib and Lenalidomide) is added to the combination of LBH-589 plus Dexamethasone in MM1S cells, the efficacy is clearly superior to the respective individual agents or double combinations. LBH-589 plus Lenalidomide displays very synergistic results with combination index (CI) less than 0.1. Although the double combinations of LBH-589 plus either Lenalidomide or Bortezomib are highly effective, the antitumor activity increased even further with triple combinations. ^[3]
Panobinostat (LBH589) + Paclitaxel(Taxol)	In the Bx-PC3 xenograft model, combination of LBH-589 with Paclitaxel results in a greater anti-tumor effect than LBH-589 alone- with 20% tumor regression and minimal cytotoxicity. ^[5]

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	LBH589 (Panobinostat) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM and 20 nM in MOLT-4 and Reh cells, respectively.
Targets	HDAC (MOLT-4 cells)	HDAC (Reh cells)
IC50	5 nM	20 nM ^[1]
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]
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]
Clinical Trials	Combined with bortezomib, LBH589 is currently in Phase III clinical trial for the treatment of patients with relapsed multiple myeloma.
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)
Formulation	Dextrose 5% in water
Dosages	10 mg/kg, 20 mg/kg
Administration	Administered via i.p. injection

References

Chemical Information

Download Panobinostat (LBH589) SDF

Molecular Weight (MW)	349.43
Formula	C₂₁H₂₃N₃O₂
CAS No.	404950-80-7, 960055-57-6 (Maleic acid), 960055-60-1 (methanesulfonate)
Synonyms	N/A

Solubility (25°C) DMSO 70 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	(E)-N-hydroxy-3-(4-((2-(2-methyl-1H-indol-3-yl)ethylamino)methyl)phenyl)acrylamide

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (9)

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Rating

Source

Breast Cancer Res Treat , 2010, 124(3), 667-675. Panobinostat (LBH589) purchased from Selleck

Method

Western blot

Cell Lines

MDA-MB-231 cells, MDA-MB-468 cells

Concentrations

0.5-10 μM

Incubation Time

24 h

Results

In both MDA-MB-231 and MDA-MB-468 cell lines, exposure to LBH589 and other compounds produced significant global increase of nuclear H3K4me2, which is the specific substrate of LSD1. The enhanced level of histone methylation by HDAC inhibitors parallels the increase of acetylation of histone 3.

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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

Breast Cancer Res Treat , 2012, 131(3), 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).

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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

Click to enlarge

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

Click to enlarge

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

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).

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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.

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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.

Product Citations (10)

Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. [Bantscheff M, et al. Nat Biotechnol 2011;29(3), 255-265]
PubMed: 21258344
KLF9 is a novel transcriptional regulator of bortezomib-and LBH589-induced apoptosis in multiple myeloma cells [Mannava S, et al. Blood 2012;119(6):1450-8]
PubMed: 22144178
A novel human high-risk ependymoma stem cell model reveals the differentiation-inducing potential of the histone deacetylase inhibitor Vorinostat. [Milde T, et al. Acta Neuropathol 2011;122(5):637-50]
PubMed: 21863243

Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. [Landreville S, et al. Clin Cancer Res 2012;18(2), 408-416]
PubMed: 22038994
DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination. [Du Z, et al. Sci Signal 2010;3(146), ra80]
PubMed: 21045206
Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. [Huang Y, et al. Breast Cancer Res Treat 2012;131(3), 777-789]
PubMed: 21452019
Knockdown of MTDH sensitizes endometrial cancer cells to cell death induction by death receptor ligand TRAIL and HDAC inhibitor LBH589 co-treatment. [Meng X, et al. PloS ONE 2011;6(6), e20920]
PubMed: 21687633
Inhibition of Histone deacetylases 1 and 6 enhances cytarabine-induced apoptosis in pediatric acute myeloid leukemia cells. [Xu X, et al. PLoS One 2011;6(2), e17138]
PubMed: 21359182
Low dose histone deacetylase inhibitor, LBH589, potentiates anticancer effect of docetaxel in epithelial ovarian cancer via PI3K/Akt pathway. [Chao H, et al. Cancer Lett 2013;329(1):17-26]
PubMed: 22995071
Induction of TAp63 by histone deacetylase inhibitors. [Sayan BS, et al. Biochem Bioph Res Co 2010;391(4), 1748-1751]
PubMed: 20043870

Tech Support & FAQs

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.

Handling Instructions

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Panobinostat (LBH589)