panobinostat Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
histone deacetylase inhibitors	4682	404950-80-7

Description:

Molecule	Description
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: 2.64 LIPINSKI: 0 HAC: 5 HDO: 4 TPSA: 77.15 ALOGS: -5.25 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
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

Approvals:

Date	Agency	Company	Orphan
Aug. 28, 2015	EMA
Feb. 23, 2015	FDA	NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Plasma cell myeloma	206.13	38.50	70	1415	44408	46640169
Malignant neoplasm progression	87.13	38.50	42	1443	64884	46619693
Diarrhoea	82.24	38.50	94	1391	559508	46125069
Platelet count decreased	80.68	38.50	46	1439	99978	46584599
Thrombocytopenia	58.64	38.50	41	1444	126540	46558037
Death	46.52	38.50	55	1430	335493	46349084
Plasmacytoma	38.55	38.50	10	1475	2467	46682110

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Plasma cell myeloma	211.33	34.90	91	1862	53371	29897154
Diarrhoea	100.40	34.90	115	1838	333988	29616537
Platelet count decreased	90.67	34.90	66	1887	106063	29844462
Malignant neoplasm progression	85.50	34.90	55	1898	72232	29878293
Morganella infection	49.92	34.90	10	1943	375	29950150
Bronchial haemorrhage	43.56	34.90	10	1943	719	29949806
Thrombocytopenia	37.02	34.90	45	1908	136999	29813526

Pharmacologic Action:

Source	Code	Description
ATC	L01XH03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Histone deacetylase (HDAC) inhibitors
FDA MoA	N0000175071	Histone Deacetylase Inhibitors
FDA EPC	N0000175588	Histone Deacetylase Inhibitor
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D056572	Histone Deacetylase Inhibitors
FDA MoA	N0000182137	Cytochrome P450 2D6 Inhibitors
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:61115	hdac inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Multiple myeloma	indication	109989006	DOID:9538
Primary cutaneous T-cell lymphoma	indication	400122007

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.83	acidic
pKa2	13.3	acidic
pKa3	9.33	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 10MG BASE	FARYDAK	SECURA	N205353	Feb. 23, 2015	RX	CAPSULE	ORAL	Feb. 23, 2022	TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 2 PRIOR REGIMENS, INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT
EQ 15MG BASE	FARYDAK	SECURA	N205353	Feb. 23, 2015	RX	CAPSULE	ORAL	Feb. 23, 2022	TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 2 PRIOR REGIMENS, INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT
EQ 20MG BASE	FARYDAK	SECURA	N205353	Feb. 23, 2015	RX	CAPSULE	ORAL	Feb. 23, 2022	TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 2 PRIOR REGIMENS, INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Histone deacetylase 7	Enzyme	Q8WUI4	HDAC7_HUMAN	INHIBITOR	Ki	8.64		CHEMBL	DRUG LABEL
Histone deacetylase 11	Enzyme	Q96DB2	HDA11_HUMAN	INHIBITOR	Ki	8.46		CHEMBL	DRUG LABEL
Histone deacetylase 8	Enzyme	Q9BY41	HDAC8_HUMAN	INHIBITOR	Ki	7.66		CHEMBL	DRUG LABEL
Histone deacetylase 9	Enzyme	Q9UKV0	HDAC9_HUMAN	INHIBITOR	Ki	8.92		CHEMBL	DRUG LABEL
Histone deacetylase 6	Enzyme	Q9UBN7	HDAC6_HUMAN	INHIBITOR	Ki	9.15		CHEMBL	DRUG LABEL
Histone deacetylase 1	Enzyme	Q13547	HDAC1_HUMAN	INHIBITOR	Ki	9		CHEMBL	DRUG LABEL
Histone deacetylase 4	Enzyme	P56524	HDAC4_HUMAN	INHIBITOR	Ki	9.22		CHEMBL	DRUG LABEL
Histone deacetylase 3	Enzyme	O15379	HDAC3_HUMAN	INHIBITOR	Ki	8.96		CHEMBL	DRUG LABEL
Histone deacetylase 2	Enzyme	Q92769	HDAC2_HUMAN	INHIBITOR	Ki	9.19		CHEMBL	DRUG LABEL
Histone deacetylase 10	Enzyme	Q969S8	HDA10_HUMAN	INHIBITOR	Ki	7.51		CHEMBL	DRUG LABEL
Histone deacetylase 5	Enzyme	Q9UQL6	HDAC5_HUMAN	INHIBITOR	Ki	9.15		CHEMBL	DRUG LABEL
Histone deacetylase	Enzyme		Q9XYC7_PLAFA		IC50	8.74		CHEMBL

External reference:

ID	Source
D10019	KEGG_DRUG
960055-56-5	SECONDARY_CAS_RN
4034263	VANDF
C3892978	UMLSCUI
CHEBI:85991	CHEBI
LBH	PDB_CHEM_ID
CHEMBL483254	ChEMBL_ID
CHEMBL3545368	ChEMBL_ID
D000077767	MESH_DESCRIPTOR_UI
DB06603	DRUGBANK_ID
7489	IUPHAR_LIGAND_ID
8805	INN_ID
9647FM7Y3Z	UNII
6918837	PUBCHEM_CID
1603349	RXNORM
232927	MMSL
30903	MMSL
d08348	MMSL
015928	NDDF
015929	NDDF
429068009	SNOMEDCT_US
429398005	SNOMEDCT_US
734519004	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
FARYDAK	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0650	CAPSULE	10 mg	ORAL	NDA	30 sections
FARYDAK	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0651	CAPSULE	15 mg	ORAL	NDA	30 sections
FARYDAK	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0652	CAPSULE	20 mg	ORAL	NDA	30 sections
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