Identification

Name
Panobinostat
Accession Number
DB06603
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • (2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]acrylamide
  • panobinostat
Product Ingredients
IngredientUNIICASInChI Key
Panobinostat hydrateD07V79Q44TNot AvailableYUKVPQZUSANPNW-ASTDGNLGSA-N
Panobinostat lactateHN0T99OO4V960055-56-5XVDWNSFFSMWXJJ-ASTDGNLGSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FarydakCapsule15 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule10 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule20 mg/1OralNovartis2015-02-23Not applicableUs
FarydakCapsule20 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule15 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule10 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule15 mg/1OralNovartis2015-02-23Not applicableUs
FarydakCapsule20 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule15 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
FarydakCapsule10 mgOralNovartis Europharm Limited2015-08-28Not applicableEu
Categories
UNII
9647FM7Y3Z
CAS number
404950-80-7
Weight
Average: 349.434
Monoisotopic: 349.179026993
Chemical Formula
C21H23N3O2
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
N-hydroxy(2E)-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enimidic acid
SMILES
[H]\C(=C(\[H])C1=CC=C(CNCCC2=C(C)NC3=CC=CC=C23)C=C1)C(O)=NO

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.

Associated Conditions
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.

TargetActionsOrganism
AHistone deacetylase
inhibitor
Human
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
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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineThe serum concentration of 4-Methoxyamphetamine can be increased when it is combined with Panobinostat.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Panobinostat.
AcetaminophenThe serum concentration of Panobinostat can be increased when it is combined with Acetaminophen.
AcetazolamideThe metabolism of Panobinostat can be decreased when combined with Acetazolamide.
Acetyl sulfisoxazoleThe metabolism of Panobinostat can be decreased when combined with Acetyl sulfisoxazole.
AcetylcholineThe serum concentration of Acetylcholine can be increased when it is combined with Panobinostat.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Panobinostat.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Panobinostat.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Panobinostat.
AjmalineThe serum concentration of Ajmaline can be increased when it is combined with Panobinostat.
Food Interactions
No interactions found.

References

General References
  1. 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. [PubMed:16428510]
  2. 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. [PubMed:26362997]
  3. Link [Link]
  4. Drugs of the Future - Panobinostat [Link]
External Links
KEGG Drug
D10019
PubChem Compound
6918837
PubChem Substance
310264874
ChemSpider
5294028
BindingDB
29589
ChEBI
85990
ChEMBL
CHEMBL483254
PharmGKB
PA166161307
HET
LBH
Drugs.com
Drugs.com Drug Page
Wikipedia
Panobinostat
ATC Codes
L01XX42 — Panobinostat
PDB Entries
5ef8
FDA label
Download (772 KB)
MSDS
Download (227 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnBasic ScienceCancer, Breast1
1Active Not RecruitingOtherNasopharyngeal Carcinoma, Lymphomas, Any EBV+ Solid Tumour1
1Active Not RecruitingTreatmentAdvanced Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentChronic Myelomonocytic Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1Active Not RecruitingTreatmentMelanoma / Skin Cancers1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1Active Not RecruitingTreatmentMultiple Myeloma in Relapse1
1Active Not RecruitingTreatmentNon-Secretory Plasma Cell Myeloma / Plasma Cell Myeloma / Plasmacytosis / Recurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1Active Not RecruitingTreatmentPlasma Cell Myeloma1
1Active Not RecruitingTreatmentSickle Cell Disorders1
1CompletedNot AvailableAdvanced Solid Tumors2
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentAdvanced Solid Tumors / Cancers1
1CompletedTreatmentCancer Patients With Advanced Solid Tumors Including Lymphoma or Chronic Hematological Malignancies1
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentCancers1
1CompletedTreatmentChronic Myelomonocytic Leukemia (CMML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS)1
1CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Tumors1
1CompletedTreatmentEsophageal Cancers / Head & Neck Cancer / Prostate Cancer1
1CompletedTreatmentHER-2 Positive Breast Cancer / Metastatic Breast Cancer (MBC)1
1CompletedTreatmentHead and Neck Carcinoma / Lung Cancers1
1CompletedTreatmentHodgkins Disease (HD) / Lymphoblastic Leukemia, Acute, Childhood / Myelogenous Leukemia, Acute, Childhood / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1CompletedTreatmentLeukemias1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Mesothelioma1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Tumors, Solid1
1CompletedTreatmentMalignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm1
1CompletedTreatmentMalignant Melanoma / Melanoma1
1CompletedTreatmentMantle Cell Lymphoma (MCL)1
1CompletedTreatmentMultiple Myeloma (MM)2
1CompletedTreatmentNeoplasms / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentProstate Cancer1
1CompletedTreatmentTumors, Solid1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1RecruitingTreatmentColorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer / Colorectal Cancer, Non-small Cell Lung Carcinoma (Adenocarcinoma), Triple Negative Breast Cancer, Renal Cell Carcinoma / Colorectal Cancers / Non-small Cell Lung Carcinoma (Adenocarcinoma) / Triple Negative Breast Cancer (TNBC)1
1RecruitingTreatmentDiffuse Intrinsic Pontine Glioma (DIPG)1
1RecruitingTreatmentGliomas1
1RecruitingTreatmentIdiopathic Myelofibrosis / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia-Vera Myelofibrosis1
1RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1TerminatedTreatmentBrain Metastasis / High-grade Meningioma / Recurrent Gliomas1
1TerminatedTreatmentHormone Refractory Prostate Cancer1
1TerminatedTreatmentHormone Refractory Prostate Cancer Disease1
1TerminatedTreatmentLiver Cancer1
1TerminatedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
1TerminatedTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
1TerminatedTreatmentMetastatic Colon Cancer / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage IV Rectal Cancer1
1TerminatedTreatmentMultiple Myeloma (MM)1
1TerminatedTreatmentTumors, Solid1
1Unknown StatusTreatmentChordomas1
1Unknown StatusTreatmentHepatocellular,Carcinoma1
1Unknown StatusTreatmentLymphoma, Hodgkins1
1WithdrawnTreatmentLung Cancers1
1, 2Active Not RecruitingTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / B-cell Adult Acute Lymphoblastic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Nodal marginal zone B-cell lymphomas / Post-Transplant Lymphoproliferative Disorder / Primary Central Nervous System Non-Hodgkin Lymphoma / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Refractory Multiple Myeloma / Splenic Marginal Zone Lymphoma / T-cell Adult Acute Lymphoblastic Leukemia / Waldenström's Macroglobulinemia (WM)1
1, 2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia1
1, 2Active Not RecruitingTreatmentCancer, Breast1
1, 2Active Not RecruitingTreatmentKahler Disease / Multiple Myeloma (MM) / Myeloma, Plasma-Cell / Plasma Cell Myeloma1
1, 2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
1, 2CompletedTreatmentAcute Myeloblastic Leukemia1
1, 2CompletedTreatmentGraft Versus Host Disease (GVHD)1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1, 2CompletedTreatmentLeukemias / Malignant Lymphomas / Multiple Myeloma (MM)1
1, 2CompletedTreatmentLymphoma, Hodgkins1
1, 2CompletedTreatmentMalignant Gliomas1
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentMetastatic Melanoma1
1, 2CompletedTreatmentMultiple Myeloma (MM)1
1, 2CompletedTreatmentProstate Cancer / Prostatic Neoplasms1
1, 2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2TerminatedTreatmentCancer, Breast1
1, 2TerminatedTreatmentCancer, Breast / Neoplasms, Breast / Tumors, Breast1
1, 2TerminatedTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
1, 2Unknown StatusTreatmentPolycythemia Vera, Post-Polycythemic Myelofibrosis Phase / Post-Essential Thrombocythemia Related Myelofibrosis / Primary Myelofibrosis1
1, 2WithdrawnTreatmentMultiple Myeloma (MM)1
2Active Not RecruitingBasic ScienceLymphoma in Leukemic Phase / Lymphoma With Cutaneous Involvement / Marrow Involvement With Lymphoma / Multiple Myeloma (MM) / Nodal Lymphoma1
2Active Not RecruitingTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Nodal marginal zone B-cell lymphomas / Peripheral T-Cell Lymphoma (PTCL) / Post-Transplant Lymphoproliferative Disorder / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Waldenström's Macroglobulinemia (WM)1
2Active Not RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)2
2Active Not RecruitingTreatmentNeoplasms, Hematologic1
2Active Not RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
2CompletedPreventionProstate Cancer1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Refractory Leukemia1
2CompletedTreatmentAdult Lymphocyte Depletion Hodgkin Lymphoma / Adult Lymphocyte Predominant Hodgkin Lymphoma / Adult Mixed Cellularity Hodgkin Lymphoma / Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma / Adult Nodular Sclerosis Hodgkin Lymphoma / Recurrent Adult Hodgkin's Lymphoma1
2CompletedTreatmentAnaplastic Large Cell Lymphoma (ALCL) (ALK-1 Negative) / Angioimmunoblastic T-Cell Lymphoma / Enteropathy- Type T-cell Lymphoma / Extranodal NK/T-cell Lymphoma Nasal Type / Hepatosplenic T-Cell Lymphoma / Peripheral T-cell Lymphoma (Not Otherwise Specified) / Relapsed ALCL (ALK-1 Positive) Post Autologous Transplant1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentClassical Hodgkin's Lymphoma (i.e. Nodular Sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte-depleted)1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentMultiple Myeloma in Relapse / Refractory Multiple Myeloma / Relapsed and Bortezomib Refractory Multiple Myeloma1
2CompletedTreatmentNeuroendocrine Tumors1
2CompletedTreatmentPost-Essential Thrombocytopenia / Post-Polycythaemia Vera / Primary Myelofibrosis1
2CompletedTreatmentRenal Cell Adenocarcinoma1
2CompletedTreatmentSmall Cell Lung Carcinoma1
2CompletedTreatmentSoft Tissue Sarcoma (STS)1
2CompletedTreatmentThyroid Carcinoma1
2Not Yet RecruitingTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2RecruitingPreventionGraft Versus Host Disease (GVHD)1
2RecruitingTreatmentDiffuse Intrinsic Pontine Glioma (DIPG) / Gliomas1
2RecruitingTreatmentMultiple Myeloma (MM)3
2RecruitingTreatmentRelapse/Refractory Multiple Myeloma1
2TerminatedNot AvailableRecurrent Malignant Gliomas1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia, B-Cell / Leukemia, T-Cell / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentAdult T-cell lymphomas/leukaemias / Cutaneous T-Cell Lymphoma (CTCL)1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentLeukemias1
2TerminatedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2TerminatedTreatmentMalignant Neoplasm of Pancreas1
2TerminatedTreatmentMetastatic Gastric Cancers1
2TerminatedTreatmentMultiple Myeloma (MM)2
2TerminatedTreatmentMyelodysplastic Syndrome1
2TerminatedTreatmentMyelodysplastic Syndromes (MDS)2
2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2WithdrawnTreatmentChronic Graft Versus Host Disease1
2WithdrawnTreatmentMalignant Lymphomas1
2WithdrawnTreatmentMultiple Myeloma (MM)1
2WithdrawnTreatmentRecurrent Glioblastoma1
2, 3CompletedTreatmentChronic Myeloid Leukemia (CML)1
2, 3CompletedTreatmentChronic Myeloid Leukemia in Chronic Phase1
2, 3CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL)2
3CompletedTreatmentLymphoma, Hodgkins1
3CompletedTreatmentMultiple Myeloma (MM)1
Not AvailableAvailableNot AvailableMultiple Myeloma (MM)1
Not AvailableNo Longer AvailableNot AvailableMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral10 mg
CapsuleOral10 mg/1
CapsuleOral15 mg
CapsuleOral15 mg/1
CapsuleOral20 mg/1
CapsuleOral20 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7067551No2001-08-312021-08-31Us
US6833384No2001-09-302021-09-30Us
US8883842No2008-06-132028-06-13Us
US6552065No2001-08-312021-08-31Us
US7989494No2008-01-172028-01-17Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000834 mg/mLALOGPS
logP3.28ALOGPS
logP1.54ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)5.45ChemAxon
pKa (Strongest Basic)10.01ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area80.64 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity106.02 m3·mol-1ChemAxon
Polarizability40.54 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Cinnamic acid or derivatives / Tryptamine / 3-alkylindole / Indole / Benzylamine / Phenylmethylamine / Styrene / Aralkylamine / Benzenoid / Substituted pyrrole
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
secondary amino compound, hydroxamic acid, cinnamamides, methylindole (CHEBI:85990)

Targets

Kind
Protein group
Organism
Human
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
  1. 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. [PubMed:17455259]
  2. 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. [PubMed:17145876]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  1. 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. [PubMed:26503877]
  2. 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. [PubMed:26504410]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:26503877]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  1. 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. [PubMed:26504410]

Drug created on March 19, 2008 10:40 / Updated on October 01, 2018 16:45