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

Stem definition	Drug id	CAS RN
ecteinascidin derivatives	4633	114899-77-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: ecteinascidin 743 ET-743 ET 743 trabectedin yondelis ecteinascidin ecteinascidine	A complex structure that includes isoquinolines joined by a cyclic ester; it is a DNA-binding agent and guanine N2 alkylator derived from the marine tunicate, Ecteinascidia turbinata. Trabectedin is used for the treatment of advanced soft-tissue SARCOMA, after failure of ANTHRACYCLINES or IFOSFAMIDE drug therapy. Molecular weight: 761.84 Formula: C39H43N3O11S CLOGP: 2.76 LIPINSKI: 2 HAC: 14 HDO: 4 TPSA: 168.72 ALOGS: -3.37 ROTB: 4 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

ecteinascidin 743
ET-743
ET 743
trabectedin
yondelis
ecteinascidin
ecteinascidine

A complex structure that includes isoquinolines joined by a cyclic ester; it is a DNA-binding agent and guanine N2 alkylator derived from the marine tunicate, Ecteinascidia turbinata. Trabectedin is used for the treatment of advanced soft-tissue SARCOMA, after failure of ANTHRACYCLINES or IFOSFAMIDE drug therapy.

Molecular weight: 761.84
Formula: C39H43N3O11S
CLOGP: 2.76
LIPINSKI: 2
HAC: 14
HDO: 4
TPSA: 168.72
ALOGS: -3.37
ROTB: 4

Status: OFP

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

Drug dosage:

None

ADMET properties:

Property	Value	Reference
Vd (Volume of distribution)	25 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	12 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.06 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	44 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company
Sept. 4, 2015	PMDA
Oct. 23, 2015	FDA	JANSSEN PRODS
Sept. 17, 2007	EMA	Pharma Mar S.A.

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
Neutropenia	260.11	45.89	137	2831	174868	63311186
Febrile neutropenia	181.93	45.89	95	2873	118354	63367700
Pancytopenia	163.93	45.89	83	2885	96850	63389204
Thrombocytopenia	139.58	45.89	87	2881	151070	63334984
Anaemia	107.64	45.89	97	2871	293333	63192721
Rhabdomyolysis	105.67	45.89	48	2920	43903	63442151
Blood creatine phosphokinase increased	98.49	45.89	41	2927	30389	63455665
Alanine aminotransferase increased	86.28	45.89	56	2912	103714	63382340
Aspartate aminotransferase increased	75.70	45.89	49	2919	90228	63395826
Leukopenia	72.40	45.89	45	2923	77245	63408809
Acute myeloid leukaemia	65.37	45.89	26	2942	17121	63468933
Neutrophil count decreased	60.93	45.89	36	2932	56370	63429684
Capillary leak syndrome	54.93	45.89	14	2954	2186	63483868
Transaminases increased	50.33	45.89	26	2942	31341	63454713
Lymphangioleiomyomatosis	46.36	45.89	8	2960	184	63485870

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
Rhabdomyolysis	76.26	43.49	41	1258	68122	34887510
Pancytopenia	73.67	43.49	45	1254	95112	34860520
Haematotoxicity	64.15	43.49	20	1279	8174	34947458
Hepatotoxicity	55.29	43.49	23	1276	21462	34934170
Alanine aminotransferase increased	49.45	43.49	33	1266	80782	34874850
Aspartate aminotransferase increased	47.13	43.49	30	1269	67753	34887879
Neutrophil count decreased	46.82	43.49	27	1272	51077	34904555
Transaminases increased	44.16	43.49	21	1278	26802	34928830

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
Pancytopenia	193.40	42.03	111	3627	165634	79575016
Neutropenia	191.48	42.03	135	3603	287575	79453075
Febrile neutropenia	147.87	42.03	106	3632	230893	79509757
Rhabdomyolysis	133.38	42.03	74	3664	103057	79637593
Thrombocytopenia	126.18	42.03	102	3636	265157	79475493
Anaemia	106.86	42.03	117	3621	444898	79295752
Alanine aminotransferase increased	102.43	42.03	74	3664	162496	79578154
Neutrophil count decreased	98.91	42.03	59	3679	93900	79646750
Aspartate aminotransferase increased	91.64	42.03	65	3673	138576	79602074
Leukopenia	89.66	42.03	60	3678	116453	79624197
Haematotoxicity	82.43	42.03	30	3708	15489	79725161
Transaminases increased	80.41	42.03	42	3696	51701	79688949
Hepatotoxicity	75.02	42.03	40	3698	51312	79689338
Platelet count decreased	74.15	42.03	66	3672	194598	79546052
Blood creatine phosphokinase increased	68.19	42.03	41	3697	66049	79674601
Capillary leak syndrome	60.17	42.03	17	3721	3908	79736742
Acute myeloid leukaemia	53.53	42.03	27	3711	30858	79709792
Hepatic function abnormal	52.24	42.03	36	3702	73071	79667579
White blood cell count decreased	51.10	42.03	53	3685	188235	79552415
Device related infection	45.29	42.03	25	3713	34269	79706381
Hypertransaminasaemia	45.10	42.03	18	3720	11906	79728744

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01CX01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS Other plant alkaloids and natural products
FDA MoA	N0000000236	Alkylating Activity
FDA EPC	N0000175558	Alkylating Drug
MeSH PA	D000477	Alkylating Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D018906	Antineoplastic Agents, Alkylating
MeSH PA	D009676	Noxae
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:67079	anti-inflammatory agents
CHEBI has role	CHEBI:76507	marine metabolites

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

Disease	Relation	SNOMED_ID	DOID
Liposarcoma	indication	254829001	DOID:3382
Malignant tumor of ovary	indication	363443007	DOID:2394
Leiomyosarcoma	indication	443719001	DOID:1967
Soft or Connective Tissue Sarcoma	indication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.18	acidic
pKa2	10.36	acidic
pKa3	10.93	acidic
pKa4	8.21	Basic
pKa5	7.59	Basic
pKa6	1.0	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
1MG/VIAL	YONDELIS	JANSSEN PRODS	N207953	Oct. 23, 2015	RX	POWDER	INTRAVENOUS	April 23, 2023	PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		IC50	6.68		CHEMBL
Nuclear receptor subfamily 1 group I member 2	Nuclear hormone receptor		NR1I2_MOUSE	ANTAGONIST	IC50	8.52		IUPHAR

External reference:

ID	Source
D06199	KEGG_DRUG
4035010	VANDF
CHEBI:84050	CHEBI
ECT	PDB_CHEM_ID
CHEMBL450449	ChEMBL_ID
CHEMBL1224207	ChEMBL_ID
2774	IUPHAR_LIGAND_ID
8206	INN_ID
DB05109	DRUGBANK_ID
ID0YZQ2TCP	UNII
1716278	RXNORM
165758	MMSL
26244	MMSL
d07398	MMSL
012537	NDDF
432214004	SNOMEDCT_US
433127001	SNOMEDCT_US
C1311070	UMLSCUI
D000077606	MESH_DESCRIPTOR_UI
108150	PUBCHEM_CID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
YONDELIS	HUMAN PRESCRIPTION DRUG LABEL	1	59676-610	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.05 mg	INTRAVENOUS	NDA	29 sections