U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H23N3O2
Molecular Weight 349.4262
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PANOBINOSTAT

SMILES

CC1=C(CCNCC2=CC=C(\C=C\C(=O)NO)C=C2)C3=C(N1)C=CC=C3

InChI

InChIKey=FPOHNWQLNRZRFC-ZHACJKMWSA-N
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+

HIDE SMILES / InChI
Molecular Formula C21H23N3O2
Molecular Weight 349.4262
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB06603

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 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.

CNS Activity

Originator

Novartis
173
Curator's Comment: # Novartis

Approval Year

2015
471
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 280.0 nM [IC50]
Inhibitor
8297
 11.0 nM [IC50]
Inhibitor
8297
 2.1 nM [IC50]
Inhibitor
8297
 13.0 nM [IC50]
Inhibitor
8297
 2.5 nM [IC50]
Inhibitor
8297
 200.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
FARYDAK

Approved Use

FARYDAK, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent

Launch Date

1.42456324E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.3 ng/mL
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/27226420
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: BORTEZOMIB
BORTEZOMIB
 PANOBINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
95.2 ng × h/mL
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/27226420
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: BORTEZOMIB
BORTEZOMIB
 PANOBINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
16.7 h
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/27226420
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: BORTEZOMIB
BORTEZOMIB
 PANOBINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
PANOBINOSTAT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
34 mg/m2 3 times / week multiple, oral
Highest studied dose|RP2D
Dose: 34 mg/m2, 3 times / week
Route: oral
Route: multiple
Dose: 34 mg/m2, 3 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/32338562
unhealthy, 1-21 years
n = 11
Health Status: unhealthy
Condition: relapsed and refractory hematologic malignancies
Age Group: 1-21 years
Sex: M+F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/32338562
DLT: Hypertriglyceridemia...
Dose limiting toxicities:
Hypertriglyceridemia (grade 4, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/32338562
15 mg/m2 1 times / week multiple, intravenous (starting)
Dose: 15 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 15 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/29987369
unhealthy, 3-17 years
n = 9
Health Status: unhealthy
Condition: refractory solid tumors
Age Group: 3-17 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/29987369
DLT: Electrocardiogram T wave abnormal...
Dose limiting toxicities:
Electrocardiogram T wave abnormal (2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/29987369
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Disc. AE: Diarrhea, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Diarrhea (17 patients)
Thrombocytopenia (6 patients)
Fatigue (11 patient)
Asthenia (11 patient)
Peripheral neuropathy (14 patients)
Thrombocytopenia (28%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
DLT: Gamma glutamyl transpeptidase increased...
Other AEs: Thrombocytopenia, Leukopenia...
Dose limiting toxicities:
Gamma glutamyl transpeptidase increased (grade 3, 1 patient)
Other AEs:
Thrombocytopenia (grade 3-4, 2 patients)
Leukopenia (grade 3-4, 2 patients)
Neutropenia (grade 3-4, 5 patients)
Nausea (grade 1-2, 4 patients)
Stomatitis (grade 1-2, 3 patients)
Vomiting (grade 1-2, 3 patients)
Fatigue (grade 3-4, 1 patient)
Fever (grade 1-2, 4 patients)
Decreased appetite (grade 1-2, 5 patients)
Hypoalbuminemia (grade 1-2, 2 patients)
Rash (grade 1-2, 3 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
Other AEs: Diarrhea, Arrhythmia...
Other AEs:
Diarrhea (severe|grade 5, 25%)
Arrhythmia (severe)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Hypertriglyceridemia grade 4, 1 patient
DLT
34 mg/m2 3 times / week multiple, oral
Highest studied dose|RP2D
Dose: 34 mg/m2, 3 times / week
Route: oral
Route: multiple
Dose: 34 mg/m2, 3 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/32338562
unhealthy, 1-21 years
n = 11
Health Status: unhealthy
Condition: relapsed and refractory hematologic malignancies
Age Group: 1-21 years
Sex: M+F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/32338562
Electrocardiogram T wave abnormal 2 patients
DLT
15 mg/m2 1 times / week multiple, intravenous (starting)
Dose: 15 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 15 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/29987369
unhealthy, 3-17 years
n = 9
Health Status: unhealthy
Condition: refractory solid tumors
Age Group: 3-17 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/29987369
Asthenia 11 patient
Disc. AE
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Fatigue 11 patient
Disc. AE
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Peripheral neuropathy 14 patients
Disc. AE
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Diarrhea 17 patients
Disc. AE
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Thrombocytopenia 28%
Disc. AE
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Thrombocytopenia 6 patients
Disc. AE
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Co-administed with::
bortezomib(1.3 mg/m2)
dexamethasone
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
unhealthy, 60 years (range: 28-79 years)
n = 386
Health Status: unhealthy
Age Group: 60 years (range: 28-79 years)
Sex: M+F
Population Size: 386
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf
Page: p. 36, 45
Hypoalbuminemia grade 1-2, 2 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Rash grade 1-2, 3 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Stomatitis grade 1-2, 3 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Vomiting grade 1-2, 3 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Fever grade 1-2, 4 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Nausea grade 1-2, 4 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Decreased appetite grade 1-2, 5 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Gamma glutamyl transpeptidase increased grade 3, 1 patient
DLT
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Fatigue grade 3-4, 1 patient
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Leukopenia grade 3-4, 2 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Thrombocytopenia grade 3-4, 2 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Neutropenia grade 3-4, 5 patients
20 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 20 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 20 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
unhealthy, 63.0 years (range: 43–75 years)
n = 8
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: 63.0 years (range: 43–75 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21964801
Arrhythmia severe
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
Diarrhea severe|grade 5, 25%
20 mg 3 times / week multiple, oral
Recommended|MTD
Dose: 20 mg, 3 times / week
Route: oral
Route: multiple
Dose: 20 mg, 3 times / week
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587

inducer
781
inducer
389

inhibitor
1767
substrate
1217

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP3A4/5
278

CYP2C19
1478

CYP1A2
1524

CYP2C8
911

CYP2E1
882

OAT1
599

OATP1B1
788

OATP1B3
706

OAT3
642

OCT1
512

OCT2
647

BCRP
699
CYP2C19
991

UGT1A1
418

UGT1A3
422

UGT1A7
236

UGT1A8
283

UGT1A9
380

UGT2B4
249

P-gp
1537

OCT1
327

OAT2
115
CYP1A1
108

CYP1A2
701

CYP2B6
547

CYP2C8
168

CYP2C19
293

CYP3A5
76

UGT1A1
69

P-gp
257

MRP2
111
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no [IC50 >100 uM]
CYP2C8
965
 no [IC50 >100 uM]
CYP2C9
1819
 no [IC50 >100 uM]
CYP2E1
970
 no [IC50 >100 uM]
BCRP
773
 no
CYP1A1
218
 no
CYP1A2
1692
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP3A4
1925
 no
CYP3A5
130
 no
OAT1
603
 no
MRP2
475
 unlikely
P-gp
1650
 unlikely
UGT1A1
254
 unlikely
CYP2C19
1553
 weak
CYP3A4
1925
 weak
CYP3A4/5
335
 weak
CYP2D6
1891
 yes [IC50 2 uM]
yes (co-administration study)
Comment: The coadministration of a single 60 mg dextromethorphan (DM) dose with FARYDAK (20 mg once per day, on Days 3, 5, and 8) increased the Cmax and AUC0-¥ of DM by 20% to 200% (interquartile range)and 20% to 130% (interquartile range), respectively
Page: 28.0
OAT3
644
 yes
OATP1B1
803
 yes
OATP1B3
715
 yes
OCT1
543
 yes
OCT2
648
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
yes (co-administration study)
Comment: In an in vivo evaluation, coadministration of a single 20 mg FARYDAK dose with the strong CYP3A4 inhibitor ketoconazole (200 mg twice daily for 14 days) increased the Cmax and AUC0-48 of PAN by 67% and 73% respectively
Page: 27.0
OAT2
115
 no
OCT1
327
 no
P-gp
1537
 yes [Km >100 uM]
CYP2C19
991
 yes
CYP2D6
1217
 yes
UGT1A1
418
 yes
UGT1A3
422
 yes
UGT1A7
236
 yes
UGT1A8
283
 yes
UGT1A9
380
 yes
UGT2B4
249
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
hERG
1647
BJB432
3
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:85990
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85990
ChemicalBook
CB61009161
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB61009161
MolPort
MolPort-005-933-338
https://www.molport.com/shop/molecule-link/MolPort-005-933-338
Selleck Chemicals
LBH-589
http://www.selleckchem.com/products/LBH-589.html
ZINC
ZINC000022010649
http://zinc15.docking.org/substances/ZINC000022010649
eMolecules
26941323
https://www.emolecules.com/cgi-bin/more?vid=26941323
PubMed

PubMed

TitleDatePubMed
Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589.
2006 Jan 15
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.
2008 Jan 15
Mitochondrial Bax translocation partially mediates synergistic cytotoxicity between histone deacetylase inhibitors and proteasome inhibitors in glioma cells.
2008 Jun
A systematic assessment of radiation dose enhancement by 5-Aza-2'-deoxycytidine and histone deacetylase inhibitors in head-and-neck squamous cell carcinoma.
2009 Mar 1
To selectivity and beyond.
2010 Dec
Induction of TAp63 by histone deacetylase inhibitors.
2010 Jan 22
Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile.
2011 Jul 14
Low-dose LBH589 increases the sensitivity of cisplatin to cisplatin-resistant ovarian cancer cells.
2011 Jun
Discovery, synthesis, and biological evaluation of novel SMN protein modulators.
2011 Sep 22
Resveratrol sensitizes acute myelogenous leukemia cells to histone deacetylase inhibitors through reactive oxygen species-mediated activation of the extrinsic apoptotic pathway.
2012 Dec
SIRT1 activation enhances HDAC inhibition-mediated upregulation of GADD45G by repressing the binding of NF-κB/STAT3 complex to its promoter in malignant lymphoid cells.
2013 May 16
Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells.
2014 May
Panobinostat for the Treatment of Multiple Myeloma.
2015 Nov 1
A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors.
2015 Sep
The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects.
2016 May 15
Patents

Patents

07989494
3
07989639
3
08536346
3
20030018062
4
20040024067
4
JP2013256542A
3

Sample Use Guides

In Vivo Use Guide
20 mg, taken orally once every other day for 3 doses per week (on Days 1, 3, 5, 8, 10, and 12) of Weeks 1 and 2 of each 21-day cycle for 8 cycles
Route of Administration: Oral
In Vitro Use Guide
Besides, Panobinostat inhibits growth of non small cell lung cancer cell lines (such as human H1299, L55 and A549 with IC50 of 5 nM, 11 nM and 30 nM, respectively), mesothelioma (such as human OK-6 and Ok-5 with IC50 of 5 nM and 7 nM, respectively) and small cell lung cancer cell lines (such as human RG-1 and LD-T with IC50 of 4 nM and 5 nM, respectively).
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:02:01 UTC 2023
Edited
by admin
on Fri Dec 15 18:02:01 UTC 2023
Record UNII
9647FM7Y3Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PANOBINOSTAT
DASH   INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
PANOBINOSTAT [MART.]
Common Name English
2-PROPENAMIDE, N-HYDROXY-3-(4-(((2-(2-METHYL-1H-INDOL-3-YL)ETHYL)AMINO)METHYL)PHENYL)-, (2E)-
Systematic Name English
PANOBINOSTAT [USAN]
Common Name English
(2E)-N-Hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enamide
Systematic Name English
Panobinostat [WHO-DD]
Common Name English
PANOBINOSTAT [MI]
Common Name English
panobinostat [INN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175588
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
FDA ORPHAN DRUG 291509
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
FDA ORPHAN DRUG 244407
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
WHO-VATC QL01XX42
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
FDA ORPHAN DRUG 705919
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
FDA ORPHAN DRUG 376212
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
WHO-ATC L01XX42
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
EU-Orphan Drug EU/3/09/721
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
NCI_THESAURUS C1946
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
Code System Code Type Description
MESH
C496932
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
EPA CompTox
DTXSID40193506
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
DRUG BANK
DB06603
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
CAS
404950-80-7
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
ChEMBL
CHEMBL483254
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
WIKIPEDIA
PANOBINOSTAT
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
USAN
YY-135
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
CHEBI
85990
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
NDF-RT
N0000182137
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
DRUG CENTRAL
4682
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
PUBCHEM
6918837
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
DAILYMED
9647FM7Y3Z
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
EVMPD
SUB31049
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
MERCK INDEX
m8383
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY Merck Index
SMS_ID
100000115952
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
NCI_THESAURUS
C66948
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
FDA UNII
9647FM7Y3Z
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
INN
8805
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
IUPHAR
7489
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY
RXCUI
1603350
Created by admin on Fri Dec 15 18:02:01 UTC 2023 , Edited by admin on Fri Dec 15 18:02:01 UTC 2023
PRIMARY RxNorm
Related Record Type Details
HISTONE DEACETYLASE 8
TARGET->WEAK INHIBITOR
IC50
CYTOCHROME P450 2D6
METABOLIC ENZYME -> INHIBITOR
OCT-1
TRANSPORTER -> INHIBITOR
Structure of PANOBINOSTAT LACTATE
SALT/SOLVATE -> PARENT
HISTONE DEACETYLASE 6
TARGET -> INHIBITOR
IC50
Structure of PANOBINOSTAT
EXCRETED UNCHANGED
URINE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
IN VITRO
HISTONE DEACETYLASE 11
TARGET -> INHIBITOR
IC50
OAT-3
TRANSPORTER -> INHIBITOR
HISTONE DEACETYLASE 5
TARGET -> INHIBITOR
IC50
CYTOCHROME P450 2D6
METABOLIC ENZYME -> SUBSTRATE
MINOR
HISTONE DEACETYLASE 2
TARGET -> INHIBITOR
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> SUBSTRATE
IN VITRO
OATP1B1
TRANSPORTER -> INHIBITOR
HISTONE DEACETYLASE 10
TARGET -> INHIBITOR
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A8
METABOLIC ENZYME -> SUBSTRATE
IN VITRO
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
HISTONE DEACETYLASE 7
TARGET->WEAK INHIBITOR
IC50
OCT-2
TRANSPORTER -> INHIBITOR
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> SUBSTRATE
IN VITRO
HISTONE DEACETYLASE 4
TARGET->WEAK INHIBITOR
IC50
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
Panobinostat is approximately 90% bound to human plasma proteins in vitro and is independent of concentration.
BINDING
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
MINOR
CYTOCHROME P450 2C19
METABOLIC ENZYME -> INHIBITOR
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A7
METABOLIC ENZYME -> SUBSTRATE
IN VITRO
OATP-8
TRANSPORTER -> INHIBITOR
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B4
METABOLIC ENZYME -> SUBSTRATE
IN VITRO
HISTONE DEACETYLASE 1
TARGET -> INHIBITOR
A PAN HDAC INHIBITOR.
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
TIME-DEPENDENT INHIBITION
HISTONE DEACETYLASE 3
TARGET -> INHIBITOR
IC50
Structure of PANOBINOSTAT HYDRATE
SOLVATE->ANHYDROUS
Structure of PANOBINOSTAT
EXCRETED UNCHANGED
FECAL
HISTONE DEACETYLASE 9
TARGET -> INHIBITOR
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
The fraction metabolized through CYP3A accounts for approximately 40% of the total hepatic panobinostat elimination.
Related Record Type Details
Structure of 4-(((2-(2-METHYL-1H-INDOL-3-YL)ETHYL)AMINO)METHYL)BENZENEACETIC ACID
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Structure of AFN-835
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Structure of 2-(4-(((2-(2-METHYL-1H-INDOL-3-YL)ETHYL)AMINO)METHYL)PHENYL)ETHAN-1-OL
METABOLITE -> PARENT
FECAL
Structure of BJB-432
METABOLITE INACTIVE -> PARENT
FECAL; PLASMA; URINE
Structure of 4-(((2-(2-METHYL-1H-INDOL-3-YL)ETHYL)AMINO)METHYL)BENZOIC ACID
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Related Record Type Details
Structure of PANOBINOSTAT
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
ORAL BIOAVAILABILITY PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC
Tmax PHARMACOKINETIC IN PATIENTS WITH ADVANCED CANCER

ORAL ADMINISTRATION

NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966