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Panobinostat

Panobinostat is a histone deacetylase (HDAC) inhibitor that has shown promise in the treatment of various cancers.
It works by altering gene expression and inducing cell cycle arrest and apoptosis in tumor cells.
Panobinostat has been evaluated in clinical trials for the treatment of multiple myeloma, lymphoma, and solid tumors.
Reserach on Panobinostat is ongoing to optimize its efficacy and safety profile for cancer therapy.

Most cited protocols related to «Panobinostat»

1
Structural Determination of HDAC Complexes
Cited 32 times
For the zCD1-TSA complex, the zCD2-TSA complex, and the zCD2-SAHA complex, X-ray diffraction data were recorded at the Stanford Synchrotron Radiation Lightsource (SSRL), beamline 14-1 (λ = 1.28184 Å). For the MBP-hCD2-TSA complex, unliganded zCD2, the H574A zCD2-substrate 8 complex, and the zCD2-Belinostat complex, X-ray diffraction data were recorded at the Advanced Photon Source (APS), beamline NE-CAT 24-ID-E (λ = 0.97918 Å). For all other structures, X-ray diffraction data were recorded at the Advanced Light Source (ALS), beamline 4.2.2 (λ = 1.00003 Å). Data reduction and integration for all datasets was achieved with HKL2000;50 data collection and reduction statistics are recorded in Supplementary Tables 2–4. Although Rmerge values were relatively high for some datasets, analysis of CC1/2 values indicated that these datasets were of sufficient quality for satisfactory structure determination and refinement.
All structures were solved by molecular replacement using the program Phaser.51 (link) For the structure of the zCD2–SAHA complex, a model of the HDAC4 catalytic domain in a closed-loop conformation (PDB entry 4CBT)52 (link) was used as the search probe for rotation and translation function calculations. For all other zCD1 and zCD2 structures, the structure of the zCD2-SAHA complex less inhibitor and water molecules was used as a search probe. For the structure determination of the fusion protein MBP-hCD2–TSA complex, maltose binding protein (PDB entry 4EDQ) and the zCD2–TSA complex less ligands and solvent molecules were used as search probes. The graphics program Coot was used for model building53 (link) and Phenix was used for crystallographic refinement.54 (link) Refinement statistics for each final model are recorded in Supplementary Tables 2–4. The quality of each model was verified with PROCHECK55 and MolProbity.56 (link) Figures were prepared with Pymol and UCSF Chimera.57 (link) The Ramachandran statistics for each model are as follows: zCD1-TSA complex: 90.3% allowed, 9.4% additionally allowed; zCD2-TSA complex: 91.6% allowed, 7.8% additionally allowed; MBP-hCD2-TSA complex: 88.5% allowed, 10.8% additionally allowed; unliganded zCD2: 91.1% allowed, 8.6% additionally allowed; H574A zCD2-substrate 8 complex: 92.2% allowed, 7.3% additionally allowed; Y785F zCD2-substrate 1 complex: 90.6% allowed, 8.7% additionally allowed; Y785F zCD2-substrate 1 complex: 90.6% allowed, 8.7% additionally allowed; zCD2-HC toxin complex: 90.6% allowed, 8.8% additionally allowed; zCD2-trifluoroketone inhibitor complex: 90.5% allowed, 9.0% additionally allowed; zCD2-acetate complex: 90.4% allowed, 9.1% additionally allowed; zCD2-SAHA complex: 91.4% allowed, 8.0% additionally allowed; zCD2-Belinostat complex: 91.1% allowed, 8.5% additionally allowed; zCD2-HPOB complex: 91.0% allowed, 8.7% additionally allowed; zCD2-Panobinostat complex: 89.9% allowed, 9.6% additionally allowed; zCD2-Oxamflatin complex: 89.3% allowed, 10.0% additionally allowed. No backbone torsion angles adopt disallowed conformations in any structure.
Hai Y, & Christianson D.W. (2016). Histone deacetylase 6 structure and molecular basis of catalysis and inhibition. Nature chemical biology, 12(9), 741-747.
Publication 2016
Acetate belinostat Catalytic Domain Chimera Crystallography HC toxin Ligands Light Maltose-Binding Proteins oxamflatin Panobinostat Proteins Radiation Solvents Vertebral Column Vorinostat X-Ray Diffraction
2
Biotin RNA Capture and Protein Analysis
Cited 15 times

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Publication 2014
Avidin Biotin Buffers Cells Dithiothreitol Edetic Acid Heparin Magnesium Chloride Malignant Neoplasms Mass Spectrometry methylstat Nonidet P-40 Panobinostat Phosphoric Monoester Hydrolases potassium thiocyanate Promega Protease Inhibitors Proteins Ribonucleases ribonuclease U RNA-Binding Proteins RNA polymerase SP6 Sodium Chloride Tromethamine Trypsin
3
Preclinical Evaluation of RMS Therapies
Cited 4 times
(Preclinical Phase I) Non-tumor bearing athymic nude mice were used for tolerability testing of the following combinations: VCR + IRN, AZD1775 + VCR + IRN, and panobinostat + bortezomib. Mice were given 4 cycles of chemotherapy with 21 days per cycle. The chemotherapeutic drug combinations and schedule used were designed to mimic potential human clinical trials. Each treatment group contained 3 mice. Vincristine was dosed by intraperitoneal injection once a week on days 1, 8, and 15. Irinotecan was dosed by intraperitoneal injection once daily on days 1–5 and 8–12. AZD1775 was dosed by oral gavage twice daily on days 1–5. Panobinostat was dosed by intraperitoneal injection once daily on days 1, 3, 5, 8, 10 and 12. Bortezomib was dosed by intraperitoneal injection once daily on days 1, 4, 8 and 11. Mouse weight and standard complete blood counts were monitored for each treatment group. The health of the animals was monitored daily throughout therapy. (Preclinical Phase II) RMS orthotopic xenografts were created by injecting luciferase labeled cells from SJRHB000026_X1 (ERMS), SJRHB012_Y (ERMS), and SJRHB013759_X1 (ARMS) into recipient CD-1 nude mice using the intramuscular injection technique previously described. Mice were screened weekly by Xenogen and the bioluminescence was measured. Mice were enrolled in the study after achieving a target bioluminescence signal of 106 –107 photons/sec/cm2 or greater for 2 weeks or a palpable tumor, and chemotherapy was started the following Monday. The following preclinical phase II trials were performed (Table S10):
Stewart E., Federico S.M., Chen X., Shelat A.A., Bradley C., Gordon B., Karlstrom A., Twarog N.R., Clay M.R., Bahrami A., Freeman BB I.I.I., Xu B., Zhou X., Wu J., Honnell V., Ocarz M., Blankenship K., Dapper J., Mardis E.R., Wilson R.K., Downing J., Zhang J., Easton J., Pappo A, & Dyer M.A. (2017). Orthotopic Patient-Derived Xenografts of Pediatric Solid Tumors. Nature, 549(7670), 96-100.
Publication 2017
Animals Arm, Upper AZD-1775 Bortezomib Cells Combination Drug Therapy Complete Blood Count Heterografts Homo sapiens Injections, Intraperitoneal Intramuscular Injection Irinotecan Luciferases Mice, Nude Mus Neoplasms Panobinostat Pharmaceutical Preparations Pharmacotherapy Therapeutics Tube Feeding Vincristine
4
DIPG Pontine Xenograft and Panobinostat CED
Cited 4 times
DIPG pontine xenografts were generated as previously described 2 (link). Briefly, a single cell suspension was made of SU-DIPG-VI-luc neurospheres and 100,000 cells (50, 000 cells/µl, 2 µl) were stereotactically injected into the fourth ventricle/pons of NOD-SCID-IL2 gamma chain-deficient cold-anesthetized postnatal day 2 mouse pups by stereotactic injection through a 31 gauge (G) burr hole (stereotactic coordinates: 3 mm posterior to lambda suture and 3 mm deep.)
CED was performed two months post-xenograft using a 31 G Hamilton with a 27 G needle threaded on the outside in isoflurane-anesthetized animals20 . (The inside needle is 1 mm longer than the outside needle in order to create the convection effects.) Infusion was performed using a digital pump set at a rate of 0.4 µl/min. Five µl of 2 µM panobinostat (SelleckChem) was delivered over a period of 12.5 min. Stereotactic coordinates (from surface of brain) used were from lambda AP −0.8mm, lateral 1 mm and 5 mm deep. Controls received vehicle (DMSO diluted in 5% dextrose). In vivo bioluminescent imaging was performed prior to CED of panobinostat or vehicle, and again 7 days later, using an IVIS imaging system (Xenogen) under isoflurane anesthesia.
Systemic administration of panobinostat was performed with intraperitoneal injection three days per week (M, W, F) for dose levels 1 mg/kg and 10 mg/kg, and administered once per week for the 20 mg/kg cohort. Controls were injected I.P with an identical volume of DMSO vehicle. Panobinostat was dissolved in 70 mg/ml DMSO, then serially diluted in water to a concentration of 0.1 to 2 mg/ml (depending on the target dose level) such that 10 µl/gram or ∼200 µl total was administered I.P each dose.
For IVIS imaging analyses of in vivo DIPG tumor growth, animals were imaged at baseline. Animals were excluded if no tumors were present, and then animals were randomized to control and treatment groups such that each group had equivalent distribution of initial tumor sizes.
Grasso C.S., Tang Y., Truffaux N., Berlow N.E., Liu L., Debily M.A., Quist M.J., Davis L.E., Huang E.C., Woo P.J., Ponnuswami A., Chen S., Johung T.B., Sun W., Kogiso M., Du Y., Lin Q., Huang Y., Hütt-Cabezas M., Warren K.E., Dret L.L., Meltzer P.S., Mao H., Quezado M., van Vuurden D.G., Abraham J., Fouladi M., Svalina M.N., Wang N., Hawkins C., Nazarian J., Alonso M.M., Raabe E., Hulleman E., Spellman P.T., Li X.N., Keller C., Pal R., Grill J, & Monje M. (2015). Functionally-defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma: A Report of the Children’s Oncology Group DIPG Preclinical Consortium. Nature medicine, 21(6), 555-559.
Publication 2015
Anesthesia Animals Brain Cells Common Cold Convection dipinacoline glutamate Fingers Gamma Rays Glucose Heterografts Injections, Intraperitoneal Isoflurane Mice, Inbred NOD Needles Neoplasms Panobinostat Pons SCID Mice Sulfoxide, Dimethyl Sutures Trephining Ventricles, Fourth
5
Panobinostat Treatment in Symptomatic Mice
Cited 3 times
Symptomatic mice (BSG GEMM) were treated with three doses of 20 mg/kg panobinostat (Selleckchem) or vehicle (25% DMSO, 0.25x PBS, 5% glucose) (n = 3 in each group) administered once daily by intraperitoneal injections. Mice were sacrificed 4 h after their final treatment via CO2. Brains from the sacrificed mice were extracted. Half of each brain was fixed in 10% formalin and embedded in paraffin for histological analysis. The other half was SNAP frozen, stored at -80 degrees and sent for pharmacokinetic (PK) studies. Pharmacokinetic analysis was performed on the cerebral cortex tissue and brainstem tumor tissue of each mouse by the Pharmacokinetic/Pharmacodynamic (PK/PD) Core Laboratory, Duke Cancer Institute as described below. Statistical significance was determined using unpaired two-tailed t-test to compare groups.
Hennika T., Hu G., Olaciregui N.G., Barton K.L., Ehteda A., Chitranjan A., Chang C., Gifford A.J., Tsoli M., Ziegler D.S., Carcaboso A.M, & Becher O.J. (2017). Pre-Clinical Study of Panobinostat in Xenograft and Genetically Engineered Murine Diffuse Intrinsic Pontine Glioma Models. PLoS ONE, 12(1), e0169485.
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Publication 2017
Brain Brain Stem Neoplasms Cortex, Cerebral Formalin Freezing Glucose Injections, Intraperitoneal Malignant Neoplasms Mice, House Panobinostat Paraffin Embedding Sulfoxide, Dimethyl Tissues

Most recents protocols related to «Panobinostat»

1
Probing PP2A-Mediated Signaling Pathways
siCtrl (#1): AllStars Neg. Control siRNA, Cat. No./ID: 1027281 (QIAGEN), siCtrl (#2): CGUACGCGGAAUACUUCGA (Eurofins), siPP2A-A: UUUUCCACUAGCUUCUUC A (Eurofins), siHRAS: GAACCCUCCUGAUGAGAGU (Eurofins), siKRAS: AGAGUGCCUUGACGAUACA (Eurofins), siNRAS: GAAAUACGCCAGUACCGAA, siPME (#1): GGAAGUGAGUCUAUAAGCA, siPME-1 (#2): UCAUAGAGGAAGAAG AAG A, siSET (#1): UGCAGACACUUGUGGAUGG (Eurofins), and siSET (#2): AAUGCA GUGCCUCUUCAUC (Eurofins). All siRNAs (CHD3, DNMT1, DOT1L, KDM1A, MLLT3, RNF168, and SMARCA4) for the cell viability assay were ordered from QIAGEN. AllStars Hs Cell Death siRNA, Cat. No./ID: 1027299 (QIAGEN), was used as a positive control (siCtrl +).
DNMT1 inhibitors (decitabine; AZA), BET inhibitors (iBET151, JQ1, mivebresib), HDAC inhibitors (panobinostat; TSA), KDM1A inhibitors (SP2509), and okadaic acid were used and purchased from SelleckChem. PP2A-reactivating compound DBK1154 was a kind gift of Dr. Michael Ohlmeyer (Atux Iskay; LCC).
Aakula A., Sharma M., Tabaro F., Nätkin R., Kamila J., Honkanen H., Schapira M., Arrowsmith C., Nykter M, & Westermarck J. (2023). RAS and PP2A activities converge on epigenetic gene regulation. Life Science Alliance, 6(5), e202301928.
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Publication 2023
Biological Assay Cell Death Cell Survival Decitabine DNMT1 protein, human DOT1L protein, human Histone Deacetylase Inhibitor inhibitors KDM1A protein, human mivebresib Okadaic Acid Panobinostat Protein Phosphatase 2A RNA, Small Interfering SMARCA4 protein, human SP2509
2
Osteoclast Differentiation Inhibitor Assay
Eagle minimal essential medium-alpha modification (α-MEM) and fetal bovine serum (FBS) were purchased from Thermo Fisher Scientific (Waltham, MA, USA). M-CSF and RANKL were procured from PeproTech EC, Ltd. (Cranbury, NJ, USA). Tartrate-resistant acid phosphatase staining kit was obtained from CosmoBio (Tokyo, Japan). Antibodies for NFATc1 (#8032s) and Cathepsin K (#48353), LSD1 (#2139), Mono-Methyl-Histone H3(Lys4) (#9723), and Mono-Methyl-Histone H3(Lys9) (#14186) were purchased from Cell Signaling Technology (Beverly, MA, USA), and β-actin antibody was purchased from Sigma-Aldrich, Inc. (St. Louis, MO, USA). GSK2879552 (molecular formula: C23H28N2O2, molecular weight: 364.5, PubChem CID: 66571643) was purchased from Selleckchem (Houston, TX, USA). GSK-LSD1 dihydrochloride (molecular formula: C14H22Cl2N2, molecular weight: 289.24, PubChem CID: 91663353) was purchased from MedChemExpress (Princeton, NJ, USA). Other epigenetic regulator inhibitors (JQ-1, ABBV-744, EPZ015866, Vorinostat, Remodelin, Panobinostat, Belinostat, Selisistat, C646, A-366, PFI-2, Tazemetostat, GSK-J4, JIB-04, and Pinometostat) were purchased from ChemScene (Monmouth Junction, NJ, USA), were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich, St. Louis, MO, USA). The structures of epigenetic regulation inhibitors corresponding to these numbers are shown in Table S1.
Ding M., Chen Z., Cho E., Park S.W, & Lee T.H. (2023). Crucial Role of Lysine-Specific Histone Demethylase 1 in RANKL-Mediated Osteoclast Differentiation. International Journal of Molecular Sciences, 24(4), 3605.
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Publication 2023
4-(4-cyanophenyl)-2-(2-cyclopentylidenehydrazinyl)thiazole ABBV-744 Actins Antibodies belinostat Cathepsin K Eagle Fetal Bovine Serum GSK-J4 GSK2879552 Histone H3 Immunoglobulins inhibitors JIB-04 KDM1A protein, human Macrophage Colony-Stimulating Factor Panobinostat selisistat SETD7 inhibitor PFI-2 Sulfoxide, Dimethyl Tartrate-Resistant Acid Phosphatase tazemetostat TNFSF11 protein, human Vorinostat
3
Caspase Activation in Ovarian Cancer
Caspase 3/7, Caspase 8, and Caspase 9 activity were measured in OVCAR3 and OVCAR8 cells lines using Caspase-Glo luminescence assays (Promega, G8091, G8201, G8211) according to the manufacturer’s specifications after exposing cells to panobinostat 10 nM alone and in combination with birinapant 20 μM for 24 h. All drug exposures occurred with or without 10 ng/mL of TNF-α. Activity data were normalized to viable cell number and measured in an identical plate by XTT assay as described.
Shibuya Y., Kudo K., Zeligs K.P., Anderson D., Hernandez L., Ning F., Cole C.B., Fergusson M., Kedei N., Lyons J., Taylor J., Korrapati S, & Annunziata C.M. (2023). SMAC Mimetics Synergistically Cooperate with HDAC Inhibitors Enhancing TNF-α Autocrine Signaling. Cancers, 15(4), 1315.
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Publication 2023
Biological Assay birinapant Caspase Caspase-7 Caspase-8 Caspase 9 Cell Lines Cells Luminescent Measurements Panobinostat Pharmaceutical Preparations Promega Tumor Necrosis Factor-alpha
4
OVCAR8 Xenograft Tumor Model
1–2 × 106 of OVCAR8 cells were counted and prepared as suspensions in 0.5 mL PBS for subcutaneous (flank) injections into 6–8 weeks old athymic nude female mice. Tumors were grown for two weeks before the mice were randomized into treatment groups. Mice then received intraperitoneal (IP) treatment with vehicle control (5% dextrose), Panobinostat 10 mg/kg, per oral (PO) treatment of tolinapant 16 mg/kg, or combination panobinostat plus tolinapant. Body weights and tumor measurements were taken twice weekly for 8–10 weeks or as required by humane endpoints. Subcutaneous tumor volumes were calculated according to the formula V = 1/2(length × width2).
Shibuya Y., Kudo K., Zeligs K.P., Anderson D., Hernandez L., Ning F., Cole C.B., Fergusson M., Kedei N., Lyons J., Taylor J., Korrapati S, & Annunziata C.M. (2023). SMAC Mimetics Synergistically Cooperate with HDAC Inhibitors Enhancing TNF-α Autocrine Signaling. Cancers, 15(4), 1315.
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Publication 2023
Body Weight Cells Glucose Injections, Intraperitoneal Mice, Nude Mus Neoplasms Panobinostat Woman
5
Cytokine Profiling of OVCAR Cell Lines
Secreted cytokine levels of IL-6, IL-8, and TNF-α were measured in culture supernatants using the Mesoscale multiplex assay after treating OVCAR3 and OVCAR8 cells overnight with Panobinostat 20 μM alone and in combination with birinapant 10 nM per manufacturer’s protocol (MesoScale Discovery, Rockville, MD, USA).
Shibuya Y., Kudo K., Zeligs K.P., Anderson D., Hernandez L., Ning F., Cole C.B., Fergusson M., Kedei N., Lyons J., Taylor J., Korrapati S, & Annunziata C.M. (2023). SMAC Mimetics Synergistically Cooperate with HDAC Inhibitors Enhancing TNF-α Autocrine Signaling. Cancers, 15(4), 1315.
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Publication 2023
Biological Assay birinapant Cells Cytokine Panobinostat Tumor Necrosis Factor-alpha

Top products related to «Panobinostat»

1
Panobinostat by Selleck Chemicals
Sourced in United States, Germany
Panobinostat is a chemical compound used in laboratory research settings. It functions as a histone deacetylase (HDAC) inhibitor. HDAC inhibitors are a class of compounds that regulate gene expression by modulating the acetylation of histones and other proteins.
2
Vorinostat by Selleck Chemicals
Sourced in United States, Germany, China
Vorinostat is a laboratory chemical compound used in research applications. It is a histone deacetylase (HDAC) inhibitor. The core function of Vorinostat is to inhibit HDAC enzymes, which play a role in gene expression regulation.
3
Dimethyl sulfoxide (dmso) by Merck Group
Sourced in United States, Germany, United Kingdom, China, Italy, Sao Tome and Principe, France, Macao, India, Canada, Switzerland, Japan, Australia, Spain, Poland, Belgium, Brazil, Czechia, Portugal, Austria, Denmark, Israel, Sweden, Ireland, Hungary, Mexico, Netherlands, Singapore, Indonesia, Slovakia, Cameroon, Norway, Thailand, Chile, Finland, Malaysia, Latvia, New Zealand, Hong Kong, Pakistan, Uruguay, Bangladesh
DMSO is a versatile organic solvent commonly used in laboratory settings. It has a high boiling point, low viscosity, and the ability to dissolve a wide range of polar and non-polar compounds. DMSO's core function is as a solvent, allowing for the effective dissolution and handling of various chemical substances during research and experimentation.
4
Romidepsin by Selleck Chemicals
Sourced in United States, China
Romidepsin is a chemical compound used as a laboratory reagent. It functions as a histone deacetylase (HDAC) inhibitor, which is a class of compounds that can alter gene expression and cellular processes.
5
Panobinostat by Novartis
Sourced in Switzerland, United States
Panobinostat is a histone deacetylase (HDAC) inhibitor. It is used as a lab research tool to study the effects of HDAC inhibition on cellular processes.
6
Panobinostat by Merck Group
Sourced in United States
Panobinostat is a histone deacetylase (HDAC) inhibitor. It is a laboratory reagent used for research purposes.
7
Panobinostat by Cayman Chemical
Sourced in United States
Panobinostat is a chemical compound used as a research tool for laboratory studies. It functions as a histone deacetylase (HDAC) inhibitor, which can be used to investigate the role of HDAC enzymes in various biological processes.
8
Entinostat by Selleck Chemicals
Sourced in United States, Germany, United Kingdom, China
Entinostat is a synthetic small molecule that functions as a histone deacetylase (HDAC) inhibitor. It is used in research and development applications involving the study of HDAC enzyme activity and its effects on gene expression.
9
Vorinostat by Merck Group
Sourced in United States, Germany, Italy
Vorinostat is a pharmaceutical compound developed by Merck Group. It is a histone deacetylase (HDAC) inhibitor used in the production of laboratory equipment and scientific research applications. The core function of Vorinostat is to regulate gene expression and cellular processes.
10
Panobinostat by LC Laboratories
Sourced in United States
Panobinostat is a non-selective histone deacetylase (HDAC) inhibitor. It is used for research purposes in the field of epigenetics and oncology.

More about "Panobinostat"

Panobinostat (also known as LBH589) is a potent histone deacetylase (HDAC) inhibitor that has shown promising results in the treatment of various types of cancer, including multiple myeloma, lymphoma, and solid tumors.
HDACs are enzymes that play a crucial role in regulating gene expression by modifying the structure of chromatin, and inhibiting their activity can lead to alterations in gene expression, cell cycle arrest, and apoptosis in tumor cells.
Panobinostat works by binding to and inhibiting HDAC enzymes, which in turn leads to the hyperacetylation of histones and other proteins.
This epigenetic modification can result in the upregulation of tumor suppressor genes and the downregulation of oncogenes, ultimately contributing to the anti-cancer effects of Panobinostat.
In clinical trials, Panobinostat has been evaluated as a single agent and in combination with other chemotherapeutic drugs, such as Vorinostat (another HDAC inhibitor) and DMSO (a solvent used in some drug formulations).
Researchers are also investigating the use of Panobinostat in combination with Romidepsin, another HDAC inhibitor, and Entinostat, a selective class I HDAC inhibitor, to optimize its efficacy and safety profile for cancer therapy.
The ongoing research on Panobinostat highlights the potential of this epigenetic-targeting drug in the field of cancer treatment.
By understanding the molecular mechanisms of Panobinostat and exploring its synergistic effects with other agents, scientists and clinicians aim to develop more effective and personalized cancer therapies that can improve patient outcomes.