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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 of ELINAFIDE

SMILES

O=C1N(CCNCCCNCCN2C(=O)C3=CC=CC4=CC=CC(C2=O)=C34)C(=O)C5=C6C(C=CC=C16)=CC=C5

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

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 TargetPharmacologyConditionPotency
18.0 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
294.3 ng/mL
24 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
105.5 ng/mL
6.6 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
22.3 ng/mL
2 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
74 ng/mL
14 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
177.8 ng/mL
18 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
47.8 ng/mL
4 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
177.1 ng/mL
10 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1357.4 ng × h/mL
24 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
384.4 ng × h/mL
6.6 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
123 ng × h/mL
2 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
658.9 ng × h/mL
14 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
978.7 ng × h/mL
18 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
238 ng × h/mL
4 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
620.6 ng × h/mL
10 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
54.6 h
24 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
42.7 h
6.6 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
39.8 h
2 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
36 h
14 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
37.3 h
18 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
37.2 h
4 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens
44.1 h
10 mg/m² 1 times / day multiple, intravenous
ELINAFIDE plasma
Homo sapiens

Doses

AEs

PubMed

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.