panobinostat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
histone deacetylase inhibitors 4682 404950-80-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • farydak
  • panobinostat lactate
  • panobinostat lactate anhydrous
  • panobinostat
  • LBH-589
  • LBH589
An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA.
  • Molecular weight: 349.43
  • Formula: C21H23N3O2
  • CLOGP: 2.42
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 4
  • TPSA: 77.15
  • ALOGS: -5.25
  • ROTB: 7
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
CL (Clearance) 10.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.10 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 13.10 hours Lombardo F, Berellini G, Obach RS
BA (Bioavailability) 30 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.193 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 3.864 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 3.622 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 8.730 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 24.960 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 36.050 % High 1
herg hERG pIC50 4.901 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 6.745 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 11.588 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 21.750 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK2,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,IGF1R,INSR,ITK,JAK1,JAK2,JAK3,KDR,KIT,MAP2K6,MAP3K21,MAP3K7,MAP4K1,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIM2,PRKCD,PRKDC,SIK2,SIK3,SRC,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ZAP70 65
kinase-selectivity-class AAK1,AKT2,AKT3,ALK,AURKC,AXL,BRAF,CAMK2D,CDK4,CDK6,CDK7,CDK9,DDR1,EPHB4,ERBB2,FLT3,GRK2,INSR,JAK2,MAP2K6,MAP3K7,MAPK12,MAPK7,MARK4,NTRK3,NUAK1,PAK4,PDK1,PDPK1,PRKCD,PRKG1,SIK2,SIK3,STK16,STK33,TEK,TNK1,ULK1,ULK2 39
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 6.138 High 1
mh-clint Mouse hepatocyte intrinsic clearance 111.944 High 1
mppb Mouse plasma protein binding (% unbound) 17.650 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 7.129 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 38.140 % High 1
rh-clint Rat hepatocyte intrinsic clearance 51.050 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 76.020 % High 1
rppb Rat plasma protein binding (% unbound) 20.040 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 568.853 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 28, 2015 EMA
Feb. 23, 2015 FDA NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 106.76 40.54 46 1439 106824 90520138
Diarrhoea 93.64 40.54 94 1391 939096 89687866
Platelet count decreased 83.81 40.54 42 1443 136927 90490035
Thrombocytopenia 72.38 40.54 44 1441 208681 90418281
Death 69.14 40.54 58 1427 456493 90170469
Plasma cell myeloma 62.77 40.54 24 1461 40804 90586158
Plasmacytoma 49.39 40.54 11 1474 2782 90624180

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 105.44 34.74 118 1898 460731 42158588
Platelet count decreased 98.58 34.74 68 1948 138513 42480806
Malignant neoplasm progression 78.86 34.74 54 1962 108346 42510973
Morganella infection 48.39 34.74 10 2006 609 42618710
Bronchial haemorrhage 47.11 34.74 10 2006 694 42618625
Thrombocytopenia 38.39 34.74 46 1970 190233 42429086
Death 36.55 34.74 73 1943 471112 42148207

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 174.31 36.19 98 3070 230345 110355786
Malignant neoplasm progression 153.31 36.19 82 3086 174485 110411646
Diarrhoea 129.59 36.19 160 3008 1139345 109446786
Thrombocytopenia 82.78 36.19 73 3095 348812 110237319
Plasma cell myeloma 76.80 36.19 37 3131 62899 110523232
Death 67.61 36.19 91 3077 698778 109887353
Plasmacytoma 49.62 36.19 14 3154 5248 110580883
White blood cell count decreased 46.46 36.19 44 3124 229346 110356785
Morganella infection 45.40 36.19 10 3158 1369 110584762
Bronchial haemorrhage 45.34 36.19 10 3158 1377 110584754

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XH03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Histone deacetylase (HDAC) inhibitors
FDA MoA N0000175071 Histone Deacetylase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D056572 Histone Deacetylase Inhibitors
FDA EPC N0000175588 Histone Deacetylase Inhibitor
FDA MoA N0000182137 Cytochrome P450 2D6 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50926 angiogenesis modulating agent
CHEBI has role CHEBI:61115 EC 3.5.1.98 (histone deacetylase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:75835 anti-anaemic agent
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

L01XH Histone deacetylase (HDAC) inhibitors 4 drugs
belinostatromidepsintucidinostatvorinostat

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538
Primary cutaneous T-cell lymphoma indication 400122007




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.83 acidic
pKa2 13.3 acidic
pKa3 9.33 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 10MG BASE FARYDAK SECURA N205353 Feb. 23, 2015 DISCN CAPSULE ORAL 8883842 June 13, 2028 TREATMENT OF MULTIPLE MYELOMA, IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE
EQ 15MG BASE FARYDAK SECURA N205353 Feb. 23, 2015 DISCN CAPSULE ORAL 8883842 June 13, 2028 TREATMENT OF MULTIPLE MYELOMA, IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE
EQ 20MG BASE FARYDAK SECURA N205353 Feb. 23, 2015 DISCN CAPSULE ORAL 8883842 June 13, 2028 TREATMENT OF MULTIPLE MYELOMA, IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Histone deacetylase 11 Enzyme INHIBITOR Ki 8.46 CHEMBL DRUG LABEL
Histone deacetylase 3 Enzyme INHIBITOR Ki 8.96 CHEMBL DRUG LABEL
Histone deacetylase 6 Enzyme INHIBITOR Ki 9.15 CHEMBL DRUG LABEL
Histone deacetylase 7 Enzyme INHIBITOR Ki 8.64 CHEMBL DRUG LABEL
Histone deacetylase 8 Enzyme INHIBITOR Ki 7.66 CHEMBL DRUG LABEL
Histone deacetylase 4 Enzyme INHIBITOR Ki 9.22 CHEMBL DRUG LABEL
Histone deacetylase 9 Enzyme INHIBITOR Ki 8.92 CHEMBL DRUG LABEL
Histone deacetylase 10 Enzyme INHIBITOR Ki 7.51 CHEMBL DRUG LABEL
Histone deacetylase 5 Enzyme INHIBITOR Ki 9.15 CHEMBL DRUG LABEL
Histone deacetylase 2 Enzyme INHIBITOR Ki 9.19 CHEMBL DRUG LABEL
Histone deacetylase 1 Enzyme INHIBITOR Ki 9 CHEMBL DRUG LABEL
Bromodomain-containing protein 4 Nuclear other IC50 8.30 CHEMBL
Phosphatidylinositol 3-kinase catalytic subunit type 3 Kinase IC50 8.30 CHEMBL
Methylcytosine dioxygenase TET2 Enzyme IC50 5.42 CHEMBL
Histone deacetylase Enzyme IC50 8.74 CHEMBL
Histone deacetylase 8 Enzyme IC50 6.35 CHEMBL
Protein Tat Transcription factor EC50 6.89 CHEMBL
Histone deacetylase Enzyme IC50 8 IUPHAR

External reference:

IDSource
D10019 KEGG_DRUG
960055-56-5 SECONDARY_CAS_RN
4034263 VANDF
CHEBI:85990 CHEBI
LBH PDB_CHEM_ID
CHEMBL483254 ChEMBL_ID
CHEMBL3545368 ChEMBL_ID
7489 IUPHAR_LIGAND_ID
8805 INN_ID
DB06603 DRUGBANK_ID
9647FM7Y3Z UNII
1603349 RXNORM
232927 MMSL
30903 MMSL
d08348 MMSL
015928 NDDF
015929 NDDF
32393311000001105 SNOMEDCT_US
429068009 SNOMEDCT_US
429398005 SNOMEDCT_US
734519004 SNOMEDCT_US
C1998098 UMLSCUI
D000077767 MESH_DESCRIPTOR_UI
6918837 PUBCHEM_CID
9647FM7Y3Z INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
FARYDAK HUMAN PRESCRIPTION DRUG LABEL 1 73116-100 CAPSULE 10 mg ORAL NDA 34 sections
FARYDAK HUMAN PRESCRIPTION DRUG LABEL 1 73116-101 CAPSULE 15 mg ORAL NDA 34 sections
FARYDAK HUMAN PRESCRIPTION DRUG LABEL 1 73116-102 CAPSULE 20 mg ORAL NDA 34 sections