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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H17N3O2.C4H6O5
Molecular Weight 417.4125
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMONAFIDE L-MALATE

SMILES

O[C@@H](CC(O)=O)C(O)=O.CN(C)CCN1C(=O)C2=CC=CC3=CC(N)=CC(C1=O)=C23

InChI

InChIKey=JNZBHHQBPHSOMU-WNQIDUERSA-N
InChI=1S/C16H17N3O2.C4H6O5/c1-18(2)6-7-19-15(20)12-5-3-4-10-8-11(17)9-13(14(10)12)16(19)21;5-2(4(8)9)1-3(6)7/h3-5,8-9H,6-7,17H2,1-2H3;2,5H,1H2,(H,6,7)(H,8,9)/t;2-/m.0/s1

HIDE SMILES / InChI

Description

Amonafide L-malate (AS1413, Xanafide) is a DNA intercalator and topoisomerase II inhibitor that induces apoptosis by disrupting chromatin organisation independently of ATP. This is different from classical topoisomerase II inhibitors which induce apoptosis by causing extensive DNA damage. Amonafide L-malate is also able to evade P-glycoprotein and related transporters that contribute to multi-drug resistance. AS1413 had orphan drug status in both the U.S. and the E.U. for the treatment of AML and also received Fast Track status from the U.S. FDA for the treatment of secondary AML. Amonafide L-malate was originated by Xanthus Pharmaceuticals. It was added to Antisoma's pipeline through the acquisition of Xanthus Pharmaceuticals, Inc. in June 2008. Antisoma discontinued development of Amonafide L-malate after data from the open-label, international Phase III ACCEDE trial in over 420 patients showed that 600 mg/m 2 IV amonafide for 5 days plus cytarabine missed the primary endpoint of significantly improving initial remission rate, defined as the proportion of patients who achieve CR or CRi, vs. daunorubicin plus cytarabine.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
5.2 μg/mL
900 mg/m² 1 times / day multiple, intravenous
NSC308847 plasma
Homo sapiens
3.25 μg/mL
1104 mg/m² single, intravenous
AMONAFIDE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1310.6 μg × min/mL
900 mg/m² 1 times / day multiple, intravenous
NSC308847 plasma
Homo sapiens
40 μg × h/mL
1800 mg/m² 1 times / day multiple, intravenous
AMONAFIDE plasma
Homo sapiens
16.64 μg × h/mL
1104 mg/m² single, intravenous
AMONAFIDE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
4.8 h
900 mg/m² 1 times / day multiple, intravenous
NSC308847 plasma
Homo sapiens
5.6 h
1800 mg/m² 1 times / day multiple, intravenous
AMONAFIDE plasma
Homo sapiens
6.7 h
1104 mg/m² single, intravenous
AMONAFIDE plasma
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
600 mg/m(2) over 4 hours on days 1 to 5
Route of Administration: Intravenous
In Vitro Use Guide
Amonafide displayed significant antitumor activities with IC50 values: 17.96 uM for HL-60, 10.67 uM for HeLa, 11.88 uM for MCF-7, 20.28 uM for LS174 and more than 50 uM for MKN45 cell lines.