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Details

Stereochemistry ACHIRAL
Molecular Formula C15H14N2O4S
Molecular Weight 318.3493
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of BELINOSTAT

SMILES

c1ccc(cc1)NS(=O)(=O)c2cccc(/C(/[H])=C(\[H])/C(=NO)O)c2

InChI

InChIKey=NCNRHFGMJRPRSK-MDZDMXLPSA-N
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+

HIDE SMILES / InChI

Molecular Formula C15H14N2O4S
Molecular Weight 318.3493
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment:: http://www.ncbi.nlm.nih.gov/pubmed/?term=16928830; http://www.ncbi.nlm.nih.gov/pubmed/?term=24800886; http://www.ncbi.nlm.nih.gov/pubmed/?term=23382909

Belinostat is a hydroxamate-type histone deacetylase inhibitor indicated for the treatment of relapsed or refractory peripheal T-cell lymphoma. The compound received orphan drug designation for the treatment of malignant thymomas. Acting on a histone deacetylase Belinostat causes the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase. PXD101 has been shown in preclinical studies to have the potential to treat a wide range of solid and hematologic malignancies either as a monotherapy or in combination with other active agents, and both an oral and intravenous formulation of the drug are being evaluated in clinical trials.

CNS Activity

Curator's Comment:: Limited penetration demonstrated on non-human primates

Originator

Curator's Comment:: Belinostat was originally filed by the CuraGen Corporation on November 15, 2004. It was transferred to Topotarget A/S in April, 2008 and then to Spectrum Pharmaceuticals on March 18, 2010.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: O15379
Gene ID: 8841
Gene Symbol: HDAC3
Target Organism: Homo sapiens (Human)
41 nM [EC50]
Target ID: Q13547
Gene ID: 3065
Gene Symbol: HDAC1
Target Organism: Homo sapiens (Human)
30 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BELEODAQ

Approved Use

Indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on tumor response rate and duration of response.

Launch Date

1404345600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
681 ng/mL
1000 mg/m² 1 times / day multiple, oral
dose: 1000 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BELINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.68 ug/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT ACID plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
21.9 ug/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
1.26 ug/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT AMIDE plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
2.1 ug/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
METHYL BELINOSTAT plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
2.56 ug/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
3-(PHENYLSULFAMOYL)BENZOIC ACID plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
80.8 ug/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT GLUCURONIDE plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
8.7 μM × h
1000 mg/m² 1 times / day multiple, oral
dose: 1000 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BELINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
361 ug*min/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT ACID plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
719 ug*min/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
647 ug*min/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT AMIDE plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
354 ug*min/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
METHYL BELINOSTAT plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
1009 ug*min/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
3-(PHENYLSULFAMOYL)BENZOIC ACID plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
15.1 mg*min/mL
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT GLUCURONIDE plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.5 h
1000 mg/m² 1 times / day multiple, oral
dose: 1000 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BELINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
131 min
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT ACID plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
118 min
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
305 min
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT AMIDE plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
79.6 min
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
METHYL BELINOSTAT plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
264 min
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
3-(PHENYLSULFAMOYL)BENZOIC ACID plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
280 min
400 mg/m^2 single, intravenous
dose: 400 mg/m^2
route of administration: intravenous
experiment type: single
co-administered:
BELINOSTAT GLUCURONIDE plasma
Homo sapiens
population: unhealthy
age: adults
sex:
food status:
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5.65%
BELINOSTAT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
DLT: Atrial fibrillation, Diarrhea...
Other AEs: Nausea, Vomiting...
Dose limiting toxicities:
Atrial fibrillation (1 patient)
Diarrhea (1 patient)
Fatigue (grade 3, 2 patients)
Other AEs:
Nausea (grade 2, 1 patient)
Vomiting (grade 2, 1 patient)
Lethargy (grade 3, 1 patient)
Diarrhea (grade 3, 1 patient)
Sources:
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
DLT: Atrial fibrillation, Vomiting...
Dose limiting toxicities:
Atrial fibrillation (1 patient)
Vomiting (1 patient)
Nausea (1 patient)
Sources:
600 mg/m2 1 times / day steady, intravenous
Dose: 600 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 600 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3)
Sources:
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Disc. AE: Fatigue, Anemia...
Other AEs: Nausea, Nausea...
AEs leading to
discontinuation/dose reduction:
Fatigue (grade 3-4, 5%)
Anemia (grade 3-4, 11%)
Febrile neutropenia
Other AEs:
Nausea (grade 1-2, 41%)
Nausea (grade 3-4, 1%)
Fatigue (grade 1-2, 32%)
Pyrexia (grade 1-2, 33%)
Pyrexia (grade 3-4, 2%)
Anemia (grade 1-2, 21%)
Vomiting (grade 1-2, 28%)
Vomiting (grade 3-4, 1%)
Constipation (grade 1-2, 22%)
Constipation (grade 3-4, 1%)
Diarrhea (grade 1-2, 21%)
Diarrhea (grade 3-4, 2%)
Dyspnea (grade 1-2, 16%)
Dyspnea (grade 3-4, 6%)
Rash (grade 1-2, 19%)
Rash (grade 3-4, 1%)
Peripheral edema (grade 1-2, 20%)
Cough (grade 1-2, 19%)
Thrombocytopenia (grade 1-2, 9%)
Thrombocytopenia (grade 3-4, 7%)
Pruritus (grade 1-2, 13%)
Pruritus (grade 3-4, 3%)
Chills (grade 1-2, 15%)
Chills (grade 3-4, 1%)
Blood lactate dehydrogenase increased (grade 1-2, 14%)
Blood lactate dehydrogenase increased (grade 3-4, 2%)
Decreased appetite (grade 1-2, 13%)
Decreased appetite (grade 3-4, 2%)
Headache (grade 1-2, 15%)
Infusion site pain (grade 1-2, 14%)
Hypokalemia (grade 1-2, 8%)
Hypokalemia (grade 3-4, 4%)
QT prolonged (grade 1-2, 7%)
QT prolonged (grade 3-4, 4%)
Abdominal pain (grade 1-2, 10%)
Abdominal pain (grade 3-4, 1%)
Hypotension (grade 1-2, 7%)
Hypotension (grade 3-4, 3%)
Phlebitis (grade 1-2, 9%)
Phlebitis (grade 3-4, 1%)
Dizziness (grade 1-2, 10%)
Tumor lysis syndrome (grade 4, 1 patient)
Pneumonia (serious|grade 5, > 2)
Sepsis (serious|grade 5, > 2)
Sources:
AEs

AEs

AESignificanceDosePopulation
Atrial fibrillation 1 patient
DLT
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Diarrhea 1 patient
DLT
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Nausea grade 2, 1 patient
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Vomiting grade 2, 1 patient
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Diarrhea grade 3, 1 patient
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Lethargy grade 3, 1 patient
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Fatigue grade 3, 2 patients
DLT
1200 mg/m2 1 times / day steady, intravenous
Highest studied dose
Dose: 1200 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1200 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Atrial fibrillation 1 patient
DLT
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Nausea 1 patient
DLT
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Vomiting 1 patient
DLT
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Fatigue grade 3
DLT
600 mg/m2 1 times / day steady, intravenous
Dose: 600 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 600 mg/m2, 1 times / day
Sources:
unhealthy, 58.5 years (range: 25-74 years)
Health Status: unhealthy
Age Group: 58.5 years (range: 25-74 years)
Sex: M+F
Sources:
Febrile neutropenia Disc. AE
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Abdominal pain grade 1-2, 10%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Dizziness grade 1-2, 10%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Decreased appetite grade 1-2, 13%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Pruritus grade 1-2, 13%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Blood lactate dehydrogenase increased grade 1-2, 14%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Infusion site pain grade 1-2, 14%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Chills grade 1-2, 15%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Headache grade 1-2, 15%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Dyspnea grade 1-2, 16%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Cough grade 1-2, 19%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Rash grade 1-2, 19%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Peripheral edema grade 1-2, 20%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Anemia grade 1-2, 21%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Diarrhea grade 1-2, 21%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Constipation grade 1-2, 22%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Vomiting grade 1-2, 28%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Fatigue grade 1-2, 32%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Pyrexia grade 1-2, 33%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Nausea grade 1-2, 41%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Hypotension grade 1-2, 7%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
QT prolonged grade 1-2, 7%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Hypokalemia grade 1-2, 8%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Phlebitis grade 1-2, 9%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Thrombocytopenia grade 1-2, 9%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Abdominal pain grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Chills grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Constipation grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Nausea grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Phlebitis grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Rash grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Vomiting grade 3-4, 1%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Anemia grade 3-4, 11%
Disc. AE
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Blood lactate dehydrogenase increased grade 3-4, 2%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Decreased appetite grade 3-4, 2%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Diarrhea grade 3-4, 2%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Pyrexia grade 3-4, 2%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Hypotension grade 3-4, 3%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Pruritus grade 3-4, 3%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Hypokalemia grade 3-4, 4%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
QT prolonged grade 3-4, 4%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Fatigue grade 3-4, 5%
Disc. AE
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Dyspnea grade 3-4, 6%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Thrombocytopenia grade 3-4, 7%
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Tumor lysis syndrome grade 4, 1 patient
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Pneumonia serious|grade 5, > 2
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Sepsis serious|grade 5, > 2
1000 mg/m2 1 times / day steady, intravenous
Recommended|MTD
Dose: 1000 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 1000 mg/m2, 1 times / day
Sources:
unhealthy, 64.0 years (range: 29-81 years)
Health Status: unhealthy
Age Group: 64.0 years (range: 29-81 years)
Sex: M+F
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes [IC50 100 uM]
yes [IC50 49.1 uM]
yes [IC50 61.8 uM]
no (co-administration study)
Comment: A human PK study was conducted in patients following the administration of the CYP2C9 substrate warfarin in the absence and presence of belinostat. The exposure of S-warfarin was not increased to a meaningful extent.
Page: 7
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101.
2003 Aug
Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies.
2006 Aug
The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo.
2007 Oct 12
Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells.
2008 Jan 15
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.
2008 Jan 15
Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implications.
2009
Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo.
2009 Mar 10
Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts.
2009 Sep
Chemical phylogenetics of histone deacetylases.
2010 Mar
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.
2011 Jul 14
Histone acetylation-mediated regulation of the Hippo pathway.
2013
Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients.
2013
Epigenetic and molecular mechanisms underlying the antileukemic activity of the histone deacetylase inhibitor belinostat in human acute promyelocytic leukemia cells.
2014 Sep
A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors.
2015 Sep
Patents

Sample Use Guides

Recommended dosage of Beleodaq is 1,000 mg/m^2 administered over 30 minutes by intravenous infusion once daily on days 1-5 of a 21-day cycle. Cycles can be repeated until disease progression or unacceptable toxicity. Treatment discontinuation or interruption with or without dosage reductions by 25% may be needed to manage adverse reactions.
Route of Administration: Intravenous
The in vitro treatment of carcinoma cell lines at 1–5 uM belinostat for 48 h caused a dose-dependent inhibition of proliferation, with the most potent inhibitory effect occurring on 5637 cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:35:29 UTC 2021
Edited
by admin
on Sat Jun 26 07:35:29 UTC 2021
Record UNII
F4H96P17NZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BELINOSTAT
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
BELINOSTAT [VANDF]
Common Name English
N-HYDROXY-3-(3-((PHENYLAMINO)SULFONYL)PHENYL)-2-PROPENAMIDE
Systematic Name English
2-PROPENAMIDE, N-HYDROXY-3-(3-((PHENYLAMINO)SULFONYL)PHENYL)-, (2E)-
Systematic Name English
NSC726630
Code English
PX-105684
Code English
BELEODAQ
Brand Name English
BELINOSTAT [USAN]
Common Name English
BELINOSTAT [ORANGE BOOK]
Common Name English
2-PROPENAMIDE, N-HYDROXY-3-(3-((PHENYLAMINO)SULFONYL)PHENYL)-
Systematic Name English
BELINOSTAT [WHO-DD]
Common Name English
PXD-101
Code English
BELINOSTAT [MI]
Common Name English
(2E)-N-HYDROXY-3-(3-(PHENYLSULFAMOYL)PHENYL)PROP-2-ENAMIDE
Systematic Name English
PXD101
Code English
BELINOSTAT [INN]
Common Name English
N-HYDROXY-3-(3-(PHENYLSULFAMOYL)PHENYL)PROP-2-ENAMIDE
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000175588
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
WHO-ATC L01XX49
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
FDA ORPHAN DRUG 289309
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
NCI_THESAURUS C1946
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
EU-Orphan Drug EU/3/13/1151
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL408513
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
NCI_THESAURUS
C48812
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
EPA CompTox
414864-00-9
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
MERCK INDEX
M2295
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY Merck Index
IUPHAR
7496
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
RXCUI
1543543
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY RxNorm
INN
8823
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
FDA UNII
F4H96P17NZ
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
DRUG CENTRAL
4876
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
CAS
866323-14-0
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
PUBCHEM
6918638
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
WIKIPEDIA
BELINOSTAT
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
CAS
414864-00-9
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
EVMPD
SUB121262
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
DRUG BANK
DB05015
Created by admin on Sat Jun 26 07:35:29 UTC 2021 , Edited by admin on Sat Jun 26 07:35:29 UTC 2021
PRIMARY
Related Record Type Details
TARGET->LIGAND
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE INACTIVE -> PARENT
MEDIATOR: UGT1A1
MAJOR
PLASMA; URINE
METABOLITE -> PARENT
The enzymes responsible for the formation of 3-(anilinosulfonyl)-benzenecarboxylic acid, (3-ASBA) are not known.
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
Belinostat also undergoes hepatic metabolism by CYP2A6, CYP2C9, and CYP3A4 enzymes to form belinostat amide and belinostat acid.
METABOLITE -> PARENT
METABOLITE -> PARENT
Belinostat also undergoes hepatic metabolism by CYP2A6, CYP2C9, and CYP3A4 enzymes to form belinostat amide and belinostat acid.
MAJOR
PLASMA; URINE
METABOLITE -> PARENT
MAJOR
PLASMA; URINE
METABOLITE INACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC