romidepsin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
depsipeptide derivatives	4119	128517-07-7

Description:

Molecule

Description

Molfile Inchi Smiles

Synonyms:

romidepsin
chromadax
istodax
FR901228
FK228

a bicyclic depsipeptide and a potent histone deacetylase inhibitor from Chromobacterium violaceum

Molecular weight: 540.69
Formula: C24H36N4O6S2
CLOGP: 3.44
LIPINSKI: 1
HAC: 10
HDO: 4
TPSA: 142.70
ALOGS: -4.41
ROTB: 2

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.64 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.20 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	7.40 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.07 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	11 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Nov. 5, 2009	FDA	CELGENE
July 3, 2017	PMDA	Celgene KK

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
Electrocardiogram QT prolonged	92.68	41.84	34	878	59496	63428614
Thrombocytopenia	59.50	41.84	33	879	151124	63336986
Platelet count decreased	58.80	41.84	30	882	116092	63372018
Tumour lysis syndrome	47.17	41.84	13	899	8977	63479133

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
Platelet count decreased	50.51	36.83	35	958	119682	34836256
Thrombocytopenia	48.61	36.83	38	955	156209	34799729

FDA Adverse Event Reporting System (Geriatric)

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
Platelet count decreased	103.03	35.88	60	1711	194604	79548013
Thrombocytopenia	85.98	35.88	60	1711	265199	79477418
Pyrexia	50.33	35.88	68	1703	678641	79063976
Tumour lysis syndrome	49.58	35.88	19	1752	23920	79718697
Atrial fibrillation	48.69	35.88	38	1733	197848	79544769
Malignant neoplasm progression	37.55	35.88	28	1743	135962	79606655
Cutaneous T-cell lymphoma	36.17	35.88	9	1762	2694	79739923

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01XH02	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	D000903	Antibiotics, Antineoplastic
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D056572	Histone Deacetylase Inhibitors
FDA MoA	N0000187061	Organic Cation Transporter 2 Inhibitors
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA	N0000190108	Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA	N0000190110	Organic Anion Transporter 1 Inhibitors
FDA MoA	N0000193845	Bile Salt Export Pump Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:61115	histone deacetylase inhibitors

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

Disease	Relation	SNOMED_ID	DOID
Peripheral T-cell lymphoma	indication	109977009
Primary cutaneous T-cell lymphoma	indication	400122007
Hypokalemia	contraindication	43339004
Conduction disorder of the heart	contraindication	44808001
Lymphocytopenia	contraindication	48813009	DOID:614
Leukopenia	contraindication	84828003	DOID:615
Chronic renal failure syndrome	contraindication	90688005
Prolonged QT interval	contraindication	111975006
Acute disease of cardiovascular system	contraindication	128487001
Hypomagnesemia	contraindication	190855004
Disease of liver	contraindication	235856003	DOID:409
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Breastfeeding (mother)	contraindication	413712001
Congenital long QT syndrome	contraindication	442917000

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	13.47	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Histone deacetylase	Enzyme	O15379 P56524 Q13547 Q8WUI4 Q92769 Q969S8 Q96DB2 Q9BY41 Q9UBN7 Q9UKV0 Q9UQL6	HDAC3_HUMAN HDAC4_HUMAN HDAC1_HUMAN HDAC7_HUMAN HDAC2_HUMAN HDA10_HUMAN HDA11_HUMAN HDAC8_HUMAN HDAC6_HUMAN HDAC9_HUMAN HDAC5_HUMAN	INHIBITOR	Ki	5.96		IUPHAR	DRUG LABEL
Histone deacetylase 2	Enzyme	Q92769	HDAC2_HUMAN		IC50	7.33		WOMBAT-PK
Histone deacetylase 1	Enzyme	Q13547	HDAC1_HUMAN		IC50	7		WOMBAT-PK
Histone deacetylase 3	Enzyme	O15379	HDAC3_HUMAN		Ki	7.60		WOMBAT-PK
Histone deacetylase 6	Enzyme	Q9UBN7	HDAC6_HUMAN		Ki	6.52		WOMBAT-PK
Histone deacetylase 7	Enzyme	Q8WUI4	HDAC7_HUMAN	INHIBITOR	Ki	5.90		IUPHAR
Histone deacetylase 8	Enzyme	Q9BY41	HDAC8_HUMAN	INHIBITOR	Ki	9.82		IUPHAR
Histone deacetylase 5	Enzyme	Q9UQL6	HDAC5_HUMAN	INHIBITOR	Ki	6.26		IUPHAR
Histone deacetylase 9	Enzyme	Q9UKV0	HDAC9_HUMAN	INHIBITOR	Ki	5.96		IUPHAR
Bromodomain-containing protein 4	Unclassified	O60885	BRD4_HUMAN		IC50	7.44		CHEMBL
Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2)	Transcription factor	O15379 Q9Y618	HDAC3_HUMAN NCOR2_HUMAN		IC50	7.74		CHEMBL
Histone deacetylase 3/NCoR1	Transcription factor	O15379 O75376	HDAC3_HUMAN NCOR1_HUMAN		Ki	9.82		CHEMBL
Histone deacetylase 4	Enzyme	P56524	HDAC4_HUMAN		IC50	6.29		WOMBAT-PK
Histone deacetylase 6	Enzyme		HDAC6_MOUSE		IC50	6.41		CHEMBL

External reference:

ID	Source
4029461	VUID
N0000180306	NUI
D06637	KEGG_DRUG
4029461	VANDF
C1527027	UMLSCUI
CHEBI:61080	CHEBI
CHEMBL343448	ChEMBL_ID
DB06176	DRUGBANK_ID
C087123	MESH_SUPPLEMENTAL_RECORD_UI
7006	IUPHAR_LIGAND_ID
8656	INN_ID
CX3T89XQBK	UNII
5352062	PUBCHEM_CID
877436	RXNORM
169125	MMSL
267261	MMSL
26838	MMSL
d07512	MMSL
013396	NDDF
444608004	SNOMEDCT_US
444737005	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Romidepsin	HUMAN PRESCRIPTION DRUG LABEL	1	0703-4004	INJECTION, SOLUTION, CONCENTRATE	5 mg	INTRAVENOUS	NDA	29 sections
Romidepsin	HUMAN PRESCRIPTION DRUG LABEL	1	0703-4004	INJECTION, SOLUTION, CONCENTRATE	5 mg	INTRAVENOUS	NDA	29 sections
Romidepsin	HUMAN PRESCRIPTION DRUG LABEL	1	0703-4004	INJECTION, SOLUTION, CONCENTRATE	5 mg	INTRAVENOUS	NDA	29 sections