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Compound Detail

CHEMBL483254

PANOBINOSTAT
💊 Approved Drug
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💊 Approved Drug
Cc1[nH]c2ccccc2c1CCNCc1ccc(/C=C/C(=O)NO)cc1

Basic Information

ChEMBL ID CHEMBL483254
Name PANOBINOSTAT
Phase Approved
Structure Type MOL
InChI Key FPOHNWQLNRZRFC-ZHACJKMWSA-N
Therapeutic ✓ Yes

Known Names

Farydak LBH-589 LBH589 Panobinostat Panobinostat hydrate
49
Targets
287
Activities
3
Assay Types
30
PK Parameters
20
Publications
5
Known Names
20
Indications

Molecular Properties

349.4
MW (Da)
3.33
ALogP
3
HBA
4
HBD
77.2
PSA (Ų)
0.23
QED
0
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2015
Availability Discontinued
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -stat
USAN Year 2011

Extended Properties

Molecular Formula C21H23N3O2
MW 349.43
Aromatic Rings 3
Heavy Atoms 26
NP-Likeness -0.44

Indications

Neoplasms Neoplasms Hodgkin Disease Hodgkin Disease Multiple Myeloma Breast Neoplasms Bronchiolitis Obliterans Syndrome Carcinoma, Renal Cell Carcinoma, Renal Cell Colorectal Neoplasms Diffuse Intrinsic Pontine Glioma Glioblastoma Glioma Graft vs Host Disease Hematologic Neoplasms Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Acute Leukemia, Plasma Cell Lymphoma

ATC Classification

L01XH03
panobinostat
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 229 meas. best 9.3
Ki 49 meas. best 10.0
EC50 9 meas. best 8.37

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone deacetylase 3
CHEMBL1829
Ki 10.0 8.8333 0.1 6
Histone deacetylase 1
CHEMBL325
IC50 9.3 8.4681 0.5 26
Histone deacetylase 1
CHEMBL325
Ki 9.27 8.645 0.5 6
Histone deacetylase 4
CHEMBL3524
Ki 9.22 6.94 0.6 5
Histone deacetylase 2
CHEMBL1937
Ki 9.19 8.49 0.7 6
Histone deacetylase 6
CHEMBL1865
Ki 9.15 8.316 0.7 5
Histone deacetylase 5
CHEMBL2563
Ki 9.15 7.6475 0.7 4
Histone deacetylase 3
CHEMBL1829
IC50 9.12 8.4313 0.8 15
Histone deacetylase
CHEMBL2093865
IC50 9.08 7.4055 0.8 11
THP-1
CHEMBL614245
IC50 9.0 9.0 1.0 1
Histone deacetylase 4
CHEMBL3524
IC50 9.0 6.7457 1.0 14
Histone deacetylase 6
CHEMBL1865
IC50 9.0 8.0524 1.0 21
Histone deacetylase 9
CHEMBL4145
Ki 8.92 6.5 1.2 4
Histone deacetylase 11
CHEMBL3310
IC50 8.8 7.22 1.6 9
Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2)
CHEMBL2111363
IC50 8.78 8.6967 1.7 6
Histone deacetylase
CHEMBL5541
IC50 8.74 8.61 1.8 2
Histone deacetylase 2
CHEMBL1937
IC50 8.7 7.9988 2.0 16
Polyamine deacetylase HDAC10
CHEMBL5103
IC50 8.7 8.1382 2.0 11
Histone deacetylase 7
CHEMBL2716
Ki 8.64 6.38 2.3 4
MV4-11
CHEMBL613835
IC50 8.53 8.53 3.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 8.47 8.275 3.4 2
Histone deacetylase 11
CHEMBL3310
Ki 8.46 7.19 3.5 2
HuT78
CHEMBL613978
EC50 8.37 8.37 4.3 1
Histone deacetylase 8
CHEMBL3192
IC50 8.31 6.8856 4.9 16
Phosphatidylinositol 3-kinase catalytic subunit type 3
CHEMBL1075165
IC50 8.3 8.3 5.0 1
Bromodomain-containing protein 4
CHEMBL1163125
IC50 8.3 8.3 5.0 1
Polyamine deacetylase HDAC10
CHEMBL5103
Ki 8.29 7.9 5.1 2
MV4-11
CHEMBL613835
EC50 8.28 8.28 5.2 1
Histone deacetylase 9
CHEMBL4145
IC50 8.24 6.975 5.7 10
Histone deacetylase 5
CHEMBL2563
IC50 8.22 7.3173 6.0 11
T47D
CHEMBL614361
IC50 8.16 8.16 7.0 1
Histone deacetylase 7
CHEMBL2716
IC50 8.09 6.341 8.2 10
NCI-N87
CHEMBL614197
IC50 8.07 8.07 8.4 1
MCF7
CHEMBL387
IC50 8.05 8.05 9.0 1
Unchecked
CHEMBL612545
EC50 8.0 7.7 10.0 2
Plasmodium falciparum
CHEMBL364
IC50 8.0 7.8667 10.0 6
CAL-27
CHEMBL1075408
IC50 7.96 7.96 10.9 1
NCI-H1975
CHEMBL614348
IC50 7.76 7.76 17.5 1
COLO 205
CHEMBL614561
IC50 7.75 7.75 18.0 1
KM3/BTZ
CHEMBL4483251
IC50 7.7 7.26 20.1 2
A549
CHEMBL392
IC50 7.7 7.7 20.0 1
Bel-7402
CHEMBL614279
IC50 7.67 7.67 21.3 1
Class 1 histone deacetylase
CHEMBL4523988
IC50 7.66 7.66 22.0 1
Histone deacetylase 8
CHEMBL3192
Ki 7.66 6.902 22.0 5
PC-3
CHEMBL390
IC50 7.62 7.62 24.0 1
EBC-1
CHEMBL4296411
IC50 7.55 7.55 27.9 1
MDA-MB-231
CHEMBL400
IC50 7.54 7.54 29.1 1
A2780
CHEMBL614004
IC50 7.46 7.36 35.0 2
HT-29
CHEMBL384
IC50 7.42 7.42 37.5 1
Unchecked
CHEMBL612545
IC50 7.34 6.3214 46.0 7

Pharmacokinetic Data

Parameter Value Units Species
AUC 273.0 ng.hr.mL-1 Mus musculus
AUC 91.3 ng.hr.mL-1 Homo sapiens
AUC 605.1 ng.hr.mL-1 Homo sapiens
AUC 356.0 ng.hr.mL-1 Homo sapiens
AUC 126.0 ng.hr.mL-1 Mus musculus
AUC 126.0 ng.hr.mL-1 Mus musculus
CL 305.0 mL.min-1.kg-1 Mus musculus
CL 0.305 mL.min-1.kg-1 Mus musculus
Cmax 31.0 nM Homo sapiens
Cmax 1410.0 nM Homo sapiens
Cmax 191.0 nM Homo sapiens
Cmax 331.97 nM Mus musculus
Cmax 331.97 nM Mus musculus
F 4.6 % Mus musculus
F 4.6 % Mus musculus
F 10.0 % Mus musculus
F 4.62 % Mus musculus
F 4.6 % Mus musculus
F 4.62 % Mus musculus
T1/2 1.37 hr Mus musculus
T1/2 12.8 hr Homo sapiens
T1/2 16.0 hr Homo sapiens
T1/2 15.0 hr Homo sapiens
T1/2 2.9 hr Mus musculus
T1/2 2.9 hr Mus musculus
T1/2 0.6833 hr Homo sapiens
T1/2 1666.67 hr Homo sapiens
T1/2 1.05 hr Homo sapiens
T1/2 37.0 hr Homo sapiens
Tmax 1.5 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone deacetylase 3 Ki = 0.1 nM 10.0 Binding affinity to HDAC3 (unknown origin) using Ac-LGKac-AMC as substrate asses... 37651268
Histone deacetylase 1 IC50 = 0.5 nM 9.3 Inhibition of HDAC1 (unknown origin) using Ac-peptide-AMC as substrate incubated... 34648295
Histone deacetylase 1 Ki = 0.54 nM 9.27 Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hr... 30122227
Histone deacetylase 4 Ki = 0.6 nM 9.22 Competitive inhibition of HDAC4 using KI-104 as substrate by fluorescence assay 21634430
Histone deacetylase 1 IC50 = 0.6 nM 9.22 Inhibition of recombinant human full-length C-terminal FLAG-tagged HDAC1 express... 31272794
Histone deacetylase 2 Ki = 0.65 nM 9.19 Inhibition of human HDAC2 20139990
Histone deacetylase 2 Ki = 0.7 nM 9.15 Inhibition of human HDAC2 25637120
Histone deacetylase 6 Ki = 0.7 nM 9.15 Competitive inhibition of HDAC6 using KI-104 as substrate by fluorescence assay 21634430
Histone deacetylase 5 Ki = 0.7 nM 9.15 Competitive inhibition of HDAC5 using KI-104 as substrate by fluorescence assay 21634430
Histone deacetylase 3 IC50 = 0.751 nM 9.12 Enzyme Assay: The inhibitory activity of panobinostat dissolved in DMSO and that... -
Histone deacetylase IC50 = 0.83 nM 9.08 Inhibition of HDAC in human HeLa cell nuclear extract using Ac-Leu-Gly-Lys (Ac)-... 27186676
Histone deacetylase 4 IC50 = 1.0 nM 9.0 Inhibition of HDAC4 (unknown origin) 37429084
Histone deacetylase 1 Ki = 1.0 nM 9.0 Inhibition of human HDAC1 20139990
Histone deacetylase 1 Ki = 1.0 nM 9.0 Inhibition of human HDAC1 25637120
Histone deacetylase 6 IC50 = 1.0 nM 9.0 Inhibition of HDAC6 (unknown origin) 37429084
THP-1 IC50 = 1.0 nM 9.0 Antiproliferative activity against human THP-1 cells assessed as inhibition of c... 37979441
Histone deacetylase 1 IC50 = 1.0 nM 9.0 Inhibition of human recombinant HDAC1 using AMC labeled AC-peptide as substrate ... 26443078
Histone deacetylase 1 IC50 = 1.0 nM 9.0 Inhibition of C-terminal His-tagged and C-terminal FLAG-tagged full length human... 27377864
Histone deacetylase 3 Ki = 1.1 nM 8.96 Inhibition of human HDAC3 25637120
Histone deacetylase 3 Ki = 1.1 nM 8.96 Inhibition of human HDAC3 20139990

Literature References

PubMed DOI Target Context # Activities
34942071 10.1021/acs.jmedchem.1c01472 ADMET 25
32940035 10.1021/acs.jmedchem.0c01541 No relevant target 15
28109947 10.1016/j.ejmech.2016.12.032 Unchecked 12
25637120 10.1016/j.bmc.2014.12.066 Homo sapiens 12
27186676 10.1021/acs.jmedchem.6b00579 NON-PROTEIN TARGET 9
30122227 10.1016/j.bmcl.2018.06.029 Unchecked 7
25637120 10.1016/j.bmc.2014.12.066 Trypanosoma brucei brucei 7
30559935 10.18632/oncotarget.26370 Histone deacetylase 6
32321249 10.1021/acs.jmedchem.0c00442 Histone deacetylase 1 6
37651268 10.1021/acs.jmedchem.3c01160 Histone deacetylase 1 6
37651268 10.1021/acs.jmedchem.3c01160 Histone deacetylase 3 6
28218840 10.1021/acs.jmedchem.6b01507 Leukotriene A-4 hydrolase 5
24471466 10.1021/jm4019542 M14 5
32321249 10.1021/acs.jmedchem.0c00442 ADMET 5
20017493 10.1021/jm901502p Mus musculus 5
32321249 10.1021/acs.jmedchem.0c00442 Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) 5
31400937 10.1016/j.bmcl.2019.08.002 Class 1 histone deacetylase 4
33691794 10.1186/s13148-021-01037-1 A549 4
33540228 10.1016/j.ejmech.2021.113213 Human immunodeficiency virus 1 4
27186676 10.1021/acs.jmedchem.6b00579 Histone deacetylase 6 4

Data from ChEMBL 36 via Core Engine