ELINAFIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C31H28N4O4
Molecular Weight	520.5784
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1N(CCNCCCNCCN2C(=O)C3=CC=CC4=C3C(=CC=C4)C2=O)C(=O)C5=CC=CC6=C5C1=CC=C6

InChI

InChIKey=QUNOQBDEVTWCTA-UHFFFAOYSA-N

InChI=1S/C31H28N4O4/c36-28-22-10-1-6-20-7-2-11-23(26(20)22)29(37)34(28)18-16-32-14-5-15-33-17-19-35-30(38)24-12-3-8-21-9-4-13-25(27(21)24)31(35)39/h1-4,6-13,32-33H,5,14-19H2

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12651198
Curator's Comment: description was created based on several sources, including: http://grantome.com/grant/NIH/M01-RR000080-40-1031 | http://adisinsight.springer.com/drugs/800005099 | https://www.ncbi.nlm.nih.gov/pubmed/7867004

Elinafide (LU 79553) is a bisintercalating naphthalamide and a topoisomerase II inhibitor has demonstrated a higher binding affinity for DNA and significant antitumour efficacy against a panel of established tumour cell lines, including several multidrug resistant-positive sublines. Elinafide had been in phase II clinical trial for the treatment of ovarian cancer and phase I trials for the treatment of various solid tumours. The major haematological toxicities observed were anaemia and neutropenia. The major non-haematological toxicities observed in the 3-weekly schedule were neuro-muscular presenting clinically as a mixed syndrome of severe weakness (sometimes with pain in both legs), myalgia and arthralgia, asthenia/fatigue/malaise. One fatality was considered related to LU 79553, as the patient had fever and neutropenia. Clinical study of this drug candidate was discontinued due to its neuromuscular dose-limiting toxicity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7867004	Inhibitor 8297		18.0 µM [IC50]
DNA 278 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10563793 \| https://www.ncbi.nlm.nih.gov/pubmed/10563793 \| https://www.ncbi.nlm.nih.gov/pubmed/19449871	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ovarian cancer 157 Sources: http://grantome.com/grant/NIH/M01-RR000080-40-1031	Primary		Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11157040	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
22.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	2 mg/m² 1 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
294.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	24 mg/m² 1 times / day multiple, intravenous dose: 24 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
47.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	4 mg/m² 1 times / day multiple, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
105.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	6.6 mg/m² 1 times / day multiple, intravenous dose: 6.6 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
177.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	10 mg/m² 1 times / day multiple, intravenous dose: 10 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
74 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	14 mg/m² 1 times / day multiple, intravenous dose: 14 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
177.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	18 mg/m² 1 times / day multiple, intravenous dose: 18 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
123 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	2 mg/m² 1 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1357.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	24 mg/m² 1 times / day multiple, intravenous dose: 24 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
238 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	4 mg/m² 1 times / day multiple, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
384.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	6.6 mg/m² 1 times / day multiple, intravenous dose: 6.6 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
620.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	10 mg/m² 1 times / day multiple, intravenous dose: 10 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
658.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	14 mg/m² 1 times / day multiple, intravenous dose: 14 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
978.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	18 mg/m² 1 times / day multiple, intravenous dose: 18 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
39.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	2 mg/m² 1 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
54.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	24 mg/m² 1 times / day multiple, intravenous dose: 24 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
37.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	4 mg/m² 1 times / day multiple, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
42.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	6.6 mg/m² 1 times / day multiple, intravenous dose: 6.6 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
44.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	10 mg/m² 1 times / day multiple, intravenous dose: 10 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
36 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	14 mg/m² 1 times / day multiple, intravenous dose: 14 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
37.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11157040	18 mg/m² 1 times / day multiple, intravenous dose: 18 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ELINAFIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
120 mg/m2 1 times / 3 weeks multiple, intravenous (unknown) MTD Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/12651198	unhealthy n = 6 Health Status: unhealthy Condition: advanced solid cancers Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12651198	DLT: neuro-muscular toxicity... Dose limiting toxicities: neuro-muscular toxicity (grade 3, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12651198

AEs

AE	Significance	Dose	Population
neuro-muscular toxicity	grade 3, 3 patients DLT	120 mg/m2 1 times / 3 weeks multiple, intravenous (unknown) MTD Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/12651198	unhealthy n = 6 Health Status: unhealthy Condition: advanced solid cancers Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12651198

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	162706-37-8	http://www.bocsci.com/description.asp?cas=162706-37-8
MuseChem	M036857	https://www.musechem.com/product/M036857.html
Synchem UG and Co KG	fd013de11	https://www.synchem.de/?s=fd013de11&post_type=product
Synchem UG and Co KG	un371	https://www.synchem.de/?s=un371&post_type=product
eMolecules	110013437	https://orderbb.emolecules.com/search/#?query=110013437

PubMed

Title	Date	PubMed
New analogues of amonafide and elinafide, containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties.	2004 Mar 11	14998328
Indirect effects modulating the interaction between DNA and a cytotoxic bisnaphthalimide reveal a two-step binding process.	2009 Jun 10	19449871
Synthesis, structural, and biological evaluation of bis-heteroarylmaleimides and bis-heterofused imides.	2011 Sep 15	21880496
Analysis of mixed DNA-bisnaphthalimide interactions involving groove association and intercalation with surface-based and solution methodologies.	2012 Dec	22987588

Patents

Sample Use Guides

In Vivo Use Guide

100 mg/m(2)/course (60 min infusion in 500 ml normal saline) (3-weekly regimen)

Route of Administration: Intravenous

In Vitro Use Guide

LU 79553 was tested in a cytotoxicity assay against a panel of human and murine cell lines. LU 79553 inhibited the growth of all cell lines tested, with EC50 values ranging from 2x10(-7) to 5x10(-10) M.

Name

Type

Language

ELINAFIDE

Official Name

English

N,N'-(TRIMETHYLENEBIS(IMINOETHYLENE))DINAPHTHALIMIDE

Common Name

English

Elinafide [WHO-DD]

Common Name

English

elinafide [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C582