Identification

Name
Belinostat
Accession Number
DB05015
Type
Small Molecule
Groups
Approved, 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
Synonyms
Not Available
External IDs
PX-105684 / PXD-101 / PXD101
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BeleodaqInjection, powder, lyophilized, for solution500 mg/10mLIntravenousSpectrum Pharmaceuticals, Inc.2014-07-21Not applicableUs
Categories
UNII
F4H96P17NZ
CAS number
866323-14-0
Weight
Average: 318.35
Monoisotopic: 318.067428113
Chemical Formula
C15H14N2O4S
InChI Key
NCNRHFGMJRPRSK-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.

TargetActionsOrganism
AHistone deacetylase
inhibitor
Human
Absorption
Not 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

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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28Not Availableextra TA in promoter, homozygousADR 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 > CADR 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
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Belinostat.Experimental
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Belinostat.Approved, Investigational
AtazanavirThe serum concentration of Belinostat can be increased when it is combined with Atazanavir.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine 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
CymarinCymarin may decrease the cardiotoxic activities of Belinostat.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Belinostat.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Belinostat.Approved, Investigational
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
GitoformateGitoformate may decrease the cardiotoxic activities of Belinostat.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Belinostat.Experimental
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Belinostat.Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Belinostat.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Belinostat.Experimental, Investigational
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
PeruvosidePeruvoside may decrease the cardiotoxic activities of Belinostat.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Belinostat.Experimental
RanolazineThe serum concentration of Belinostat can be increased when it is combined with Ranolazine.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Belinostat.Approved, Investigational
Food Interactions
Not Available

References

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
PubChem Compound
6918638
PubChem Substance
347827703
ChemSpider
5293831
BindingDB
25150
ChEBI
61076
ChEMBL
CHEMBL408513
HET
5OG
Wikipedia
Belinostat
ATC Codes
L01XX49 — Belinostat
PDB Entries
5een
FDA label
Download (308 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdult Solid Neoplasm1
1Active Not RecruitingTreatmentBlast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Leukemia Acute Myeloid Leukemia (AML) / 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
1Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL) / Peripheral T-Cell Lymphoma (PTCL)1
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) / Chronic Myelogenous Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / 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 / Neoplasms1
1CompletedTreatmentMalignant Lymphomas / Tumors, Solid1
1CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
1CompletedTreatmentTumors1
1Not Yet RecruitingTreatmentMalignant Lymphomas / Relapsed and Refractory Aggressive B- and T-cell Lymphomas1
1RecruitingTreatmentHaematological Malignancies / Tumors, Solid1
1RecruitingTreatmentRelapsed/Refractory Solid Tumors/Hematological Malignancies1
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, 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, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentStage IV Non-Small Cell Lung Cancer1
1, 2TerminatedNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (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

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous500 mg/10mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6888027No2001-09-272021-09-27Us
US8835501No2007-10-272027-10-27Us

Properties

State
Solid
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 features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Cinnamic acids and derivatives
Sub Class
Not Available
Direct Parent
Cinnamic acids and derivatives
Alternative Parents
Sulfanilides / Benzenesulfonamides / Benzenesulfonyl compounds / Styrenes / Organosulfonamides / Aminosulfonyl compounds / Hydroxamic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
show 2 more
Substituents
Cinnamic acid or derivatives / Benzenesulfonamide / Sulfanilide / Benzenesulfonyl group / Styrene / Monocyclic benzene moiety / Benzenoid / Organosulfonic acid amide / Aminosulfonyl compound / Sulfonyl
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
sulfonamide, 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 impo...

Components:
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
Substrate
Inhibitor
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 un...
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 un...
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 un...
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 November 09, 2017 03:50