Identification
NameBelinostat
Accession NumberDB05015
TypeSmall Molecule
GroupsApproved, Investigational
Description

Belinostat is a novel agent that inhibits the enzyme histone deacetylase (HDAC) with a sulfonamide-hydroxamide structure. It was developed as an orphan drug to target hematological malignancies and solid tumors by TopoTarget. The safety and efficacy of belinostat is currently being evaluated for use in combination with traditional front-line therapies for the treatment of PTCL. Intravenous administration of the agent is available as Beleodaq as monotherapy and the dosing regimen involves a 21-day cycle. It was US-approved in July 2014 as a therapeutic agent for relapsed or refractory peripheral T-cell lymphoma.

Structure
Thumb
SynonymsNot Available
External IDs PX-105684 / PXD-101 / PXD101
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BeleodaqInjection, powder, lyophilized, for solution500 mg/10mLIntravenousSpectrum Pharmaceuticals, Inc.2014-07-21Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIF4H96P17NZ
CAS number866323-14-0
WeightAverage: 318.35
Monoisotopic: 318.067428113
Chemical FormulaC15H14N2O4S
InChI KeyNCNRHFGMJRPRSK-MDZDMXLPSA-N
InChI
InChI=1S/C15H14N2O4S/c18-15(16-19)10-9-12-5-4-8-14(11-12)22(20,21)17-13-6-2-1-3-7-13/h1-11,17,19H,(H,16,18)/b10-9+
IUPAC Name
(2E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide
SMILES
ONC(=O)\C=C\C1=CC=CC(=C1)S(=O)(=O)NC1=CC=CC=C1
Pharmacology
Indication

Belinostat is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) with manageable safety profile. It is a potential alternative therapy for patients who did not experience adequate response to first-line drugs for PTCL. It can be used in patients with baseline thrombocytopenia [2].

Structured Indications
Pharmacodynamics

Beleodaq is a histone deacetylase (HDAC) inhibitor that exhibits pan-HDAC inhibition and potent growth inhibitory and pro-apoptotic activities in a variety of tumor cells, including PTCL cells, at nanomolar concentrations [2]. None of the trials show any clinically relevant changes caused by Beleodaq on heart rate, PR duration or QRS duration as measures of autonomic state, atrio-ventricular conduction or depolarization; there were no cases of Torsades de Pointes.

Mechanism of action

Belinostat inhibits the activity of histone deacetylase (HDAC) thus prevents the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, increased the expression of tumor-suppressor genes. It ultimately induces cell cycle arrest, inhibition of angiogenesis and/or apoptosis of some transformed cells.

TargetKindPharmacological actionActionsOrganismUniProt ID
Histone deacetylaseProtein groupyes
inhibitor
Humannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distribution

The volume of distribution is 409 ± 76.7 L.

Protein binding

92.9% and 95.8% of belinostat is bound to protein.

Metabolism

Primarily metabolized by hepatic UGT1A1. Strong UGT1A1 inhibitors are expected to increase exposure to belinostat. Belinostat also undergoes hepatic metabolism by CYP2A6, CYP2C9, and CYP3A4 enzymes to form belinostat amide and belinostat acid. The enzymes responsible for the formation of methyl belinostat and 3-(anilinosulfonyl)-benzenecarboxylic acid, (3-ASBA) are not known

SubstrateEnzymesProduct
Belinostat
Belinostat glucuronideDetails
Route of elimination

Approximately 40% of the belinostat dose is excreted renally, primarily as metabolites and less than 2% of total dose recovered as unchanged parent drug.

Half life

Displays a three-compartment pharmacokinetic property with elimination half life of 1.1 hours

Clearance

1240 mL/min

Toxicity

Belinostat is genotoxic according to Ames test and may impair male fertility. Weekly complete blood count should be monitored during treatment to adjust the dosage as intravenous infusion of belinostat is frequently associated with hematologic toxicity such as leukopenia and thrombocytopenia. Incidences of infections such as sepsis, hepatotoxicity, tumor lysis syndrome, gastrointestinal toxicity, and embryo-fetal toxicity may occur. No specific information is available on the treatment of overdosage of Beleodaq. There is no antidote for Beleodaq and it is not known if Beleodaq is dialyzable. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28Not Availableextra TA in promoter, homozygous ADR Directly StudiedPatients who carry this genotype in UGT1A1 are at greater risk of experiencing dose-limiting toxicity from belinostat therapy. Details
UDP-glucuronosyltransferase 1-1UGT1A1*60(C;C)A > C ADR Directly StudiedPatients who carry this genotype in UGT1A1 may be at greater risk of experiencing dose-limiting toxicity from belinostat therapy. Details
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Belinostat.Approved
AtazanavirThe serum concentration of Belinostat can be increased when it is combined with Atazanavir.Approved, Investigational
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Belinostat.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Belinostat.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Belinostat.Approved
ClozapineThe risk or severity of adverse effects can be increased when Belinostat is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Belinostat.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Belinostat.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Belinostat.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Belinostat.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Belinostat.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Belinostat.Withdrawn
OleandrinAnvirzel may decrease the cardiotoxic activities of Belinostat.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Belinostat.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Belinostat.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Belinostat.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Moskowitz AJ, Horwitz SM: Targeting histone deacetylases in T-cell lymphoma. Leuk Lymphoma. 2017 Jun;58(6):1306-1319. doi: 10.1080/10428194.2016.1247956. Epub 2016 Nov 4. [PubMed:27813438 ]
  2. Hood K, Shah A: Belinostat for Relapsed or Refractory Peripheral T-Cell Lymphoma. J Adv Pract Oncol. 2016 Mar;7(2):209-218. Epub 2016 Mar 1. [PubMed:28090369 ]
  3. Wang LZ, Ramirez J, Yeo W, Chan MY, Thuya WL, Lau JY, Wan SC, Wong AL, Zee YK, Lim R, Lee SC, Ho PC, Lee HS, Chan A, Ansher S, Ratain MJ, Goh BC: Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients. PLoS One. 2013;8(1):e54522. doi: 10.1371/journal.pone.0054522. Epub 2013 Jan 30. [PubMed:23382909 ]
  4. Valiuliene G, Stirblyte I, Cicenaite D, Kaupinis A, Valius M, Navakauskiene R: Belinostat, a potent HDACi, exerts antileukaemic effect in human acute promyelocytic leukaemia cells via chromatin remodelling. J Cell Mol Med. 2015 Jul;19(7):1742-55. doi: 10.1111/jcmm.12550. Epub 2015 Apr 11. [PubMed:25864732 ]
External Links
ATC CodesL01XX49 — Belinostat
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (308 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdult Solid Neoplasm1
1CompletedTreatmentAccelerated Phase of Disease / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA / Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Blastic Phase / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndrome / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia / Previously Treated Myelodysplastic Syndromes / Primary Myelofibrosis / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Disease / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes1
1CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Myeloid Leukaemias (AML) / Chronic Myelogenous Leukemia (CML) / Myelodysplastic Syndrome1
1CompletedTreatmentAdult Grade III Lymphomatoid Granulomatosis / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Post-Transplant Lymphoproliferative Disorder / Primary Central Nervous System Hodgkin Lymphoma / Primary Central Nervous System Non-Hodgkin Lymphoma / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell 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 / Splenic Marginal Zone Lymphoma / Stage III Adult Burkitt Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage III Adult Diffuse Mixed Cell Lymphoma / Stage III Adult Diffuse Small Cleaved Cell Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage III Adult Immunoblastic Large Cell Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage III Mantle Cell Lymphoma / Stage III Marginal Zone Lymphoma / Stage III Mycosis Fungoides/Sezary Syndrome / Stage III Small Lymphocytic Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Hodgkin Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IV Marginal Zone Lymphoma / Stage IV Mycosis Fungoides/Sezary Syndrome / Stage IV Small Lymphocytic Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Waldenstrom's Macroglobulinemia (WM)1
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentCarcinoma Neuroendocrine / Malignant Epithelial Neoplasms / Small Cell Lung Carcinoma1
1CompletedTreatmentHaematological Malignancies / Tumors, Solid1
1CompletedTreatmentMalignant Lymphomas / Tumors, Solid1
1CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
1CompletedTreatmentTumors1
1Not Yet RecruitingTreatmentMalignant Lymphomas / Relapsed and Refractory Aggressive B- and T-cell Lymphomas1
1RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL) / Peripheral T-Cell Lymphoma (PTCL)1
1RecruitingTreatmentHaematological Malignancies / Tumors, Solid1
1RecruitingTreatmentMalignant Lymphomas / Neoplasms1
1RecruitingTreatmentRelapsed/Refractory Solid Tumors/Hematological Malignancies1
1SuspendedTreatmentAcute Myeloid Leukaemias (AML) / Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Myelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Refractory Acute Myeloid Leukemia / Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Secondary Acute Myeloid Leukemia / Therapy-Related Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
1TerminatedTreatmentAdult 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 / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Post-Transplant Lymphoproliferative Disorder / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell 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 / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Stage III Adult Burkitt Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage III Adult Diffuse Mixed Cell Lymphoma / Stage III Adult Diffuse Small Cleaved Cell Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage III Adult Immunoblastic Large Cell Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage III Mantle Cell Lymphoma / Stage III Marginal Zone Lymphoma / Stage III Mycosis Fungoides/Sezary Syndrome / Stage III Small Lymphocytic Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Hodgkin Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IV Marginal Zone Lymphoma / Stage IV Mycosis Fungoides/Sezary Syndrome / Stage IV Small Lymphocytic Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Waldenstrom's Macroglobulinemia (WM)1
1WithdrawnTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentAcute Myeloid Leukaemias (AML)1
1, 2CompletedTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer1
1, 2CompletedTreatmentBladder Cancers / Cancer, Ovarian / Fallopian Tube Cancer / Ovarian Epithelial Cancer1
1, 2CompletedTreatmentDose Escalation: Solid Tumors / MTD: Soft Tissue Sarcomas1
1, 2CompletedTreatmentStage IV Non-Small Cell Lung Cancer1
1, 2TerminatedNot AvailableNon-Small-Cell Lung Carcinoma (NSCLC)1
1, 2TerminatedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
1, 2WithdrawnTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentAnaplastic Large Cell Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Mantle Cell Lymphoma1
2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Recurrent Adult Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdvanced Malignant Mesothelioma / Epithelial Mesothelioma / Recurrent Malignant Mesothelioma / Sarcomatous Mesothelioma1
2CompletedTreatmentBrenner Tumor / Fallopian Tube Cancer / Ovarian Clear Cell Cystadenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Ovarian Mixed Epithelial Carcinoma / Ovarian Mucinous Cystadenocarcinoma / Ovarian Serous Cystadenocarcinoma / Ovarian Undifferentiated Adenocarcinoma / Primary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer1
2CompletedTreatmentCarcinoma of Unknown Primary1
2CompletedTreatmentDe Novo Myelodysplastic Syndromes / Previously Treated Myelodysplastic Syndromes / Secondary Myelodysplastic Syndromes1
2CompletedTreatmentFallopian Tube Cancer / Fallopian Tube Carcinoma / Primary Peritoneal Carcinoma / Primary Peritoneal Cavity Cancer / Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor / Recurrent Ovarian Carcinoma / Recurrent Ovarian Epithelial Cancer / Stage III Borderline Ovarian Surface Epithelial-stromal Tumor / Stage III Ovarian Cancer / Stage III Ovarian Epithelial Cancer / Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor / Stage IV Ovarian Cancer / Stage IV Ovarian Epithelial Cancer1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
2CompletedTreatmentRecurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma1
2CompletedTreatmentAdvanced thymic carcinoma / Thymic Carcinoma1
2RecruitingTreatmentAdult T-cell lymphomas/leukaemias1
2RecruitingTreatmentGlioblastoma Multiforme of Brain1
2TerminatedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Non-Hodgkin's Lymphoma (NHL) / Peripheral T-Cell Lymphoma (PTCL)1
2TerminatedTreatmentMultiple Myeloma (MM)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous500 mg/10mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6888027 No2001-09-272021-09-27Us
US8835501 No2007-10-272027-10-27Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility0.14 mg/mLFDA Label
pKa7.87 and 8.71 by potentiometryFDA LABEL
Predicted Properties
PropertyValueSource
Water Solubility0.0285 mg/mLALOGPS
logP1.83ALOGPS
logP1.81ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)7.82ChemAxon
pKa (Strongest Basic)-5.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area95.5 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity83.48 m3·mol-1ChemAxon
Polarizability30.99 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cinnamic acids and derivatives. These are organic aromatic compounds containing a benzene and a carboxylic acid group (or a derivative thereof) forming 3-phenylprop-2-enoic acid.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCinnamic acids and derivatives
Sub ClassNot Available
Direct ParentCinnamic acids and derivatives
Alternative ParentsSulfanilides / Benzenesulfonamides / Benzenesulfonyl compounds / Styrenes / Organosulfonamides / Aminosulfonyl compounds / Hydroxamic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
SubstituentsCinnamic acid or derivatives / Benzenesulfonamide / Sulfanilide / Benzenesulfonyl group / Styrene / Monocyclic benzene moiety / Benzenoid / Organosulfonic acid amide / Aminosulfonyl compound / Sulfonyl
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptorssulfonamide, hydroxamic acid, olefinic compound (CHEBI:61076 )

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 important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
Components:
NameUniProt IDDetails
Histone deacetylase 1Q13547 Details
Histone deacetylase 10Q969S8 Details
Histone deacetylase 11Q96DB2 Details
Histone deacetylase 2Q92769 Details
Histone deacetylase 3O15379 Details
Histone deacetylase 4P56524 Details
Histone deacetylase 5Q9UQL6 Details
Histone deacetylase 6Q9UBN7 Details
Histone deacetylase 7Q8WUI4 Details
Histone deacetylase 8Q9BY41 Details
Histone deacetylase 9Q9UKV0 Details
References
  1. Hood K, Shah A: Belinostat for Relapsed or Refractory Peripheral T-Cell Lymphoma. J Adv Pract Oncol. 2016 Mar;7(2):209-218. Epub 2016 Mar 1. [PubMed:28090369 ]
  2. FDA Label [Link]

Enzymes

1. UDP-glucuronosyltransferase 1A1
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
References
  1. Wang LZ, Ramirez J, Yeo W, Chan MY, Thuya WL, Lau JY, Wan SC, Wong AL, Zee YK, Lim R, Lee SC, Ho PC, Lee HS, Chan A, Ansher S, Ratain MJ, Goh BC: Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients. PLoS One. 2013;8(1):e54522. doi: 10.1371/journal.pone.0054522. Epub 2013 Jan 30. [PubMed:23382909 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Uniprot Name:
Cytochrome P450 2C8
Molecular Weight:
55824.275 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Uniprot Name:
Cytochrome P450 2C9
Molecular Weight:
55627.365 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Uniprot Name:
Cytochrome P450 1A2
Molecular Weight:
58293.76 Da
References
  1. FDA Cross discipline team leader review [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Drug created on October 21, 2007 16:23 / Updated on September 01, 2017 15:53