Panobinostat (LBH589)

Catalog No.S1030 Batch:S103012

Technical Data

Formula	C₂₁H₂₃N₃O₂
Molecular Weight	349.43	CAS No.	404950-80-7
Solubility (25°C)*	In vitro	DMSO	70 mg/mL (200.32 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.

Targets

HDAC (MOLT-4 cells) ^[1]	HDAC (Reh cells) ^[1]
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]

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]

Protocol (from 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 Dosages 10 mg/kg, 20 mg/kg Administration Administered via i.p. injection

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
Dosages
10 mg/kg, 20 mg/kg
Administration
Administered via i.p. injection

References

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Customer Product Validation

: Data from [Breast Cancer Res Treat , 2012, 131, 777-789]

: Data from [PLoS One, 2011, 6, e17138]

: Data from [PLoS One, 2011, 6, e17138]

: Data from [PLoS One, 2011, 6, e20920]

Selleck's Panobinostat (LBH589) has been cited by 411 publications

Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection [ Emerg Microbes Infect, 2024, 13(1):2327371]	PubMed: 38444369
Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression [ Cell Rep, 2024, 43(1):113575]	PubMed: 38181788
Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine-induced killer cell efficiency in multiple myeloma via the NKG2D pathway [ Clin Transl Immunology, 2024, 13(3):e1500]	PubMed: 38529413
EphA2- and HDAC-Targeted Combination Therapy in Endometrial Cancer [ Int J Mol Sci, 2024, 25(2)1278]	PubMed: 38279277
HDAC Inhibition Induces CD26 Expression on Multiple Myeloma Cells via the c-Myc/Sp1-mediated Promoter Activation [ Cancer Res Commun, 2024, 4(2):349-364]	PubMed: 38284882
Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer [ Nat Commun, 2023, 14(1):6332]	PubMed: 37816716
General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis [ Nat Commun, 2023, 14(1):1392]	PubMed: 36914627
Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis [ Nat Commun, 2023, 14(1):4129]	PubMed: 37452018
Spatially controlled construction of assembloids using bioprinting [ Nat Commun, 2023, 14(1):4346]	PubMed: 37468483
The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma [ Nat Commun, 2023, 14(1):1516]	PubMed: 36934113

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SHIPPING AND STORAGE
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