Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C18H19N3O.2ClH |
| Molecular Weight | 366.285 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.CN(C)CCNC(=O)C1=CC=CC2=CC3=C(C=CC=C3)N=C12
InChI
InChIKey=WFAUJCPSRLMTBB-UHFFFAOYSA-N
InChI=1S/C18H19N3O.2ClH/c1-21(2)11-10-19-18(22)15-8-5-7-14-12-13-6-3-4-9-16(13)20-17(14)15;;/h3-9,12H,10-11H2,1-2H3,(H,19,22);2*1H
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C18H19N3O |
| Molecular Weight | 293.363 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Acridine carboxamide (XR5000) is a tricyclic acridine-based (or carboxamide-based) drug with dual topoisomerase inhibitor and potential antineoplastic activities. Acridine carboxamide inhibits both topoisomerases I and II and intercalates into DNA, resulting in DNA damage, the disruption of DNA repair and replication, the inhibition of RNA and protein synthesis, and cell death. Acridine carboxamide has been used in trials studying the treatment of lung cancer and brain and central nervous system tumors. In clinical trials acridine carboxamide did not show efficacy when tested against various types of cancers.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. | 2010-08 |
|
| In vitro assessment of novel transcription inhibitors and topoisomerase poisons in rhabdomyosarcoma cell lines. | 2009-11 |
|
| Early tumor drug pharmacokinetics is influenced by tumor perfusion but not plasma drug exposure. | 2008-12-15 |
|
| The role of topoisomerases and RNA transcription in the action of the antitumour benzonaphthyridine derivative SN 28049. | 2008-10 |
|
| Plasma pharmacokinetic evaluation of cytotoxic agents radiolabelled with positron emitting radioisotopes. | 2008-04 |
|
| Inhibition of human CYP1A2 oxidation of 5,6-dimethyl-xanthenone-4-acetic acid by acridines: a molecular modelling study. | 2005-08 |
|
| Mechanisms of action of DNA intercalating acridine-based drugs: how important are contributions from electron transfer and oxidative stress? | 2003-12 |
|
| Use of positron emission tomography in pharmacokinetic studies to investigate therapeutic advantage in a phase I study of 120-hour intravenous infusion XR5000. | 2003-01-15 |
|
| Pharmacokinetics of radiolabelled anticancer drugs for positron emission tomography. | 2003 |
|
| Inter-strain variability in aldehyde oxidase activity in the mouse. | 2002-07 |
|
| Kinetic studies of the binding of acridinecarboxamide topoisomerase poisons to DNA: implications for mode of binding of ligands with uncharged chromophores. | 2002-02-14 |
|
| Topoisomerase I/II selectivity among derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA). | 2001-12 |
|
| Effects of anticancer drugs on the metabolism of the anticancer drug 5,6-dimethylxanthenone-4-acetic (DMXAA) by human liver microsomes. | 2001-08 |
|
| Extravascular transport of the DNA intercalator and topoisomerase poison N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (DACA): diffusion and metabolism in multicellular layers of tumor cells. | 2001-06 |
|
| Comparative biodistribution and metabolism of carbon-11-labeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and DNA-intercalating analogues. | 2001-04-01 |
|
| Individual variation in hepatic aldehyde oxidase activity. | 2001-04 |
|
| Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography. | 2001-03-01 |
|
| Effects of protein binding on the in vitro activity of antitumour acridine derivatives and related anticancer drugs. | 2000 |
Patents
Sample Use Guides
Advanced ovarian cancer: Patients received Acridine carboxamide (XR5000) at the dose of 3010 mg/m(2) through a 120-h central venous infusion every 3 weeks.
Route of Administration:
Intravenous
CCRF-CEM cells were exposed to a range of concentrations of TAS-103 (0.1 to 10 uM) or Acridine carboxamide (0.1 to 100
uM) for 2 hr and then analysed using the TARDIS assay to
detect drug-stabilised topo I, topo IIa, and topo IIb cleavable complexes in individual cells. These cells were sensitive to
Acridine carboxamide and TAS-103 with IC50 values of 474 and 5 nM,
respectively. Acridine carboxamide showed a dose-dependent increase in topo IIa
FITC immunofluorescence levels, with 10 and 100
uM Acridine carboxamide giving significantly higher levels of cleavable
complexes than the untreated cells. Only
the highest concentration of 100 uM Acridine carboxamide showed any
effect on topo IIb FITC immunofluorescence. Topo IIa transformants
were found to be more sensitive (Acridine carboxamide IC50=50 uM)
than topo IIb transformants (Acridine carboxamide IC50 >137 uM).
| Substance Class |
Chemical
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| Record UNII |
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