Identification
- Summary
Panobinostat is a non-selective histone deacetylase inhibitor used to treat multiple myeloma in combination with other antineoplastic agents.
- Brand Names
- Farydak
- Generic Name
- Panobinostat
- DrugBank Accession Number
- DB06603
- Background
Panobinostat is an oral deacetylace (DAC) inhibitor approved on February 23, 2015 by the FDA for the treatment of multiple myeloma. The approval was accelerated based on progression-free survival, therefore confirmatory trials by the sponsor to demonstrate clinical efficacy in multiple myeloma treatment are in progress of being conducted. Panobinostat is marketed by Novartis under the brand name Farydak. Panobinostat acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor) and it is the most potent DAC inhibiting agent available on the market.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Panobinostat (DB06603)
- Weight
- Average: 349.434
Monoisotopic: 349.179026993 - Chemical Formula
- C21H23N3O2
- Synonyms
- (2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]acrylamide
- 2-PROPENAMIDE, N-HYDROXY-3-(4-(((2-(2-METHYL-1H-INDOL-3-YL)ETHYL)AMINO)METHYL)PHENYL)-, (2E)-
- hydroxypropyl-B-cyclodextrin-panobinostat complex
- Panobinostat
- Panobinostatum
Pharmacology
- Indication
Panobinostat is indicated in the treatment of multiple myeloma in combination with dexamethasone and bortezomib in patients who have received 2 previous treatment regimens including bortezomib and an immunomodulatory agent. This indication is approved by accelerated approval based on progression free survival as of February 23, 2015.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
Panobinostat is a deacetylase (DAC) inhibitor. DACs, also known as histone DACs (HDAC), are responsible for regulating the acetylation of about 1750 proteins in the body; their functions are involved in many biological processes including DNA replication and repair, chromatin remodelling, transcription of genes, progression of the cell-cycle, protein degradation and cytoskeletal reorganization. In multiple myeloma, there is an overexpression of DAC proteins. Panobinostat inhibits class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC 11) proteins. Panobinostat's antitumor activity is believed to be attributed to epigenetic modulation of gene expression and inhibition of protein metabolism. Panobinostat also exhibits cytotoxic synergy with bortezomib, a proteasome inhibitor concurrently used in treatment of multiple myeloma.
Target Actions Organism AHistone deacetylase inhibitorHumans - Absorption
After a 20 mg dose, panobinostat was quickly absorbed with a time to maximum absorption of 2 hours.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Panobinostat was extensively metabolized to 77 metabolites. Unchanged panobinostat recovered in urine and feces was 2% and 3%, respectively. Primary metabolic pathways of panobinostat are reduction, hydrolysis, oxidation, and glucuronidation processes. CYP and non-CYP enzymes were found to play significant role in metabolism, CYP2D6 and CYP2C19 playing minor roles.
- Route of elimination
Not Available
- Half-life
30 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Farydak carries a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram (ECG) changes have occurred in patients receiving Farydak. Because of these risks, Farydak is being approved with a Risk Evaluation and Mitigation Strategy (REMS) consisting of a communication plan to inform health care professionals of these risks and how to minimize them.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Panobinostat can be increased when it is combined with Abametapir. Abatacept The metabolism of Panobinostat can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Panobinostat. Abrocitinib The serum concentration of Panobinostat can be increased when it is combined with Abrocitinib. Acalabrutinib The metabolism of Panobinostat can be decreased when combined with Acalabrutinib. Acebutolol The metabolism of Acebutolol can be decreased when combined with Panobinostat. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Panobinostat. Acetazolamide The serum concentration of Panobinostat can be increased when it is combined with Acetazolamide. Acrivastine The risk or severity of QTc prolongation can be increased when Acrivastine is combined with Panobinostat. Adagrasib The serum concentration of Panobinostat can be increased when it is combined with Adagrasib. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of panobinostat.
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of panobinostat.
- Take at the same time every day.
- Take with a full glass of water.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Panobinostat hydrate D07V79Q44T Not Available YUKVPQZUSANPNW-ASTDGNLGSA-N Panobinostat lactate HN0T99OO4V 960055-56-5 XVDWNSFFSMWXJJ-ASTDGNLGSA-N - International/Other Brands
- Faridak / Farydak
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Farydak Capsule 10 mg Oral Zr Pharma& Gmb H 2016-09-08 Not applicable EU 
Farydak Capsule 10 mg/1 Oral Secura Bio, Inc. 2015-02-23 Not applicable US 
Farydak Capsule 20 mg/1 Oral Novartis Pharmaceuticals Corporation 2015-02-23 2022-12-31 US Farydak Capsule 20 mg Oral Zr Pharma& Gmb H 2016-09-08 Not applicable EU Farydak Capsule 20 mg/1 Oral Secura Bio, Inc. 2015-02-23 Not applicable US Farydak Capsule 15 mg Oral Zr Pharma& Gmb H 2016-09-08 Not applicable EU Farydak Capsule 10 mg Oral Zr Pharma& Gmb H 2016-09-08 Not applicable EU Farydak Capsule 15 mg/1 Oral Novartis Pharmaceuticals Corporation 2015-02-23 2022-12-31 US Farydak Capsule 20 mg Oral Zr Pharma& Gmb H 2016-09-08 Not applicable EU Farydak Capsule 15 mg/1 Oral Secura Bio, Inc. 2015-02-23 Not applicable US
Categories
- ATC Codes
- L01XH03 — Panobinostat
- Drug Categories
- Amines
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Histone deacetylase (HDAC) inhibitors
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Hydroxy Acids
- Hydroxylamines
- Immunosuppressive Agents
- Indoles
- Moderate Risk QTc-Prolonging Agents
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tryptamines and derivatives. These are compounds containing the tryptamine backbone, which is structurally characterized by an indole ring substituted at the 3-position by an ethanamine.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Tryptamines and derivatives
- Direct Parent
- Tryptamines and derivatives
- Alternative Parents
- Cinnamic acids and derivatives / 3-alkylindoles / Styrenes / Phenylmethylamines / Benzylamines / Aralkylamines / Substituted pyrroles / Heteroaromatic compounds / Hydroxamic acids / Amino acids and derivatives show 6 more
- Substituents
- 3-alkylindole / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzylamine / Carbonyl group / Carboxylic acid derivative show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- secondary amino compound, hydroxamic acid, cinnamamides, methylindole (CHEBI:85990)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 9647FM7Y3Z
- CAS number
- 404950-80-7
- InChI Key
- FPOHNWQLNRZRFC-ZHACJKMWSA-N
- InChI
- 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+
- IUPAC Name
- (2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enamide
- SMILES
- CC1=C(CCNCC2=CC=C(\C=C\C(=O)NO)C=C2)C2=CC=CC=C2N1
References
- General References
- Qian DZ, Kato Y, Shabbeer S, Wei Y, Verheul HM, Salumbides B, Sanni T, Atadja P, Pili R: Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res. 2006 Jan 15;12(2):634-42. [Article]
- Laubach JP, Moreau P, San-Miguel JF, Richardson PG: Panobinostat for the Treatment of Multiple Myeloma. Clin Cancer Res. 2015 Nov 1;21(21):4767-73. doi: 10.1158/1078-0432.CCR-15-0530. Epub 2015 Sep 11. [Article]
- Link [Link]
- Drugs of the Future - Panobinostat [Link]
- External Links
- KEGG Drug
- D10019
- PubChem Compound
- 6918837
- PubChem Substance
- 310264874
- ChemSpider
- 5294028
- BindingDB
- 29589
- 1603350
- ChEBI
- 85990
- ChEMBL
- CHEMBL483254
- ZINC
- ZINC000022010649
- PharmGKB
- PA166161307
- PDBe Ligand
- LBH
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Panobinostat
- PDB Entries
- 5ef8
- FDA label
- Download (772 KB)
- MSDS
- Download (227 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 10 mg/1 Capsule Oral 15 mg/1 Capsule Oral 20 mg/1 Capsule Oral 10 mg Capsule Oral 15 mg Capsule Oral 20 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7067551 No 2006-06-27 2021-08-31 US US6833384 No 2004-12-21 2021-09-30 US US8883842 No 2014-11-11 2028-06-13 US US6552065 No 2003-04-22 2021-08-31 US US7989494 No 2011-08-02 2028-01-17 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00198 mg/mL ALOGPS logP 3.16 ALOGPS logP 2.48 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 9.31 Chemaxon pKa (Strongest Basic) 9.95 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 77.15 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 105.5 m3·mol-1 Chemaxon Polarizability 38.94 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transcription regulatory region sequence-specific dna binding
- Specific Function
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Components:
References
- Beckers T, Burkhardt C, Wieland H, Gimmnich P, Ciossek T, Maier T, Sanders K: Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer. 2007 Sep 1;121(5):1138-48. [Article]
- Geng L, Cuneo KC, Fu A, Tu T, Atadja PW, Hallahan DE: Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res. 2006 Dec 1;66(23):11298-304. [Article]
- Favreau AJ, McGlauflin RE, Duarte CW, Sathyanarayana P: miR-199b, a novel tumor suppressor miRNA in acute myeloid leukemia with prognostic implications. Exp Hematol Oncol. 2016 Feb 3;5:4. doi: 10.1186/s40164-016-0033-6. eCollection 2015. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Richardson PG, Harvey RD, Laubach JP, Moreau P, Lonial S, San-Miguel JF: Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: pharmacology and clinical outcomes. Expert Rev Clin Pharmacol. 2016;9(1):35-48. doi: 10.1586/17512433.2016.1096773. Epub 2015 Oct 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Richardson PG, Harvey RD, Laubach JP, Moreau P, Lonial S, San-Miguel JF: Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: pharmacology and clinical outcomes. Expert Rev Clin Pharmacol. 2016;9(1):35-48. doi: 10.1586/17512433.2016.1096773. Epub 2015 Oct 26. [Article]
- Bailey H, Stenehjem DD, Sharma S: Panobinostat for the treatment of multiple myeloma: the evidence to date. J Blood Med. 2015 Oct 8;6:269-76. doi: 10.2147/JBM.S69140. eCollection 2015. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Bailey H, Stenehjem DD, Sharma S: Panobinostat for the treatment of multiple myeloma: the evidence to date. J Blood Med. 2015 Oct 8;6:269-76. doi: 10.2147/JBM.S69140. eCollection 2015. [Article]
Drug created at March 19, 2008 16:40 / Updated at July 18, 2023 22:56