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Details

Stereochemistry ACHIRAL
Molecular Formula C15H18N2O4
Molecular Weight 290.3144
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of Apaziquone hydroquinone

SMILES

CN1C(\C=C\CO)=C(CO)C2=C1C(O)=CC(N3CC3)=C2O

InChI

InChIKey=HXBAQKBYZCLYEZ-NSCUHMNNSA-N
InChI=1S/C15H18N2O4/c1-16-10(3-2-6-18)9(8-19)13-14(16)12(20)7-11(15(13)21)17-4-5-17/h2-3,7,18-21H,4-6,8H2,1H3/b3-2+

HIDE SMILES / InChI

Description
Curator's Comment: the description was created based on several sources, including https://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=42095 | https://www.drugs.com/history/qapzola.html | https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM520094.pdf

Apaziquone (EOquin, EO9) is an indolequinone that is a bioreductive prodrug and a chemical analog of the older chemotherapeutic agent mitomycin C. In hypoxic cells, such as those on the inner surface of the urinary bladder, apaziquone is converted to active metabolites by intracellular reductases (such as NQO1). The active metabolites alkylate DNA and lead to apoptosis. In animal tumour models, EO9 was inactive against the P388 murine leukaemia but exhibited anti-tumour activity against human tumour xenografts and the generally chemo-resistant murine adenocarcinomas of the colon (MAC) tumours. Initial evidence that in vivo response correlated with NQO1 activity. Apaziquone was selected for clinical evaluation based upon its novel mechanism of action (which was distinct from MMC), its preferential activity against cells derived from solid tumours in vitro and in vivo, its ability to target both aerobic and hypoxic cells and the lack of myelosuppression in mice and rats. Apaziquone has been applied in clinical studies sponsored by Spectrum Pharmaceuticals and Allergan, Inc. for the treatment of superficial (non-muscle invasive) bladder cancer. However, the US-FDA determined that it was not statistically effective.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2311221
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
4 mg 6 times / week multiple, intravesical (unknown)
Studied dose
Dose: 4 mg, 6 times / week
Route: intravesical
Route: multiple
Dose: 4 mg, 6 times / week
Sources:
unhealthy
n = 53
Health Status: unhealthy
Condition: bladder cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 53
Sources:
Disc. AE: pollakisuria...
AEs leading to
discontinuation/dose reduction:
pollakisuria (1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
pollakisuria 1 pt
Disc. AE
4 mg 6 times / week multiple, intravesical (unknown)
Studied dose
Dose: 4 mg, 6 times / week
Route: intravesical
Route: multiple
Dose: 4 mg, 6 times / week
Sources:
unhealthy
n = 53
Health Status: unhealthy
Condition: bladder cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 53
Sources:
PubMed

PubMed

TitleDatePubMed
Increased tumor necrosis factor-alpha sensitivity of MCF-7 cells transfected with NAD(P)H:quinone reductase.
2000 Jul 1
Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies.
2008 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Irrigation of bladder via catheter.
Either one or two instillations of 4 mg/40 mL apaziquone are given by intravesical administration into the bladder at 60±30 minutes post Transurethral Resection of Bladder Tumor via an indwelling 100% Silicone Foley catheter.
Route of Administration: Irrigation
In Vitro Use Guide
Breast (HBL 100, MCF7, MDA 231), small cell lung cancer (H249, N417, H526, H841), non- small cell lung cancer (AS49, H226, H322, H358, H460) and colon (HT29) cell lines were used for activity evaluation in MTT assay. Initial experiments to determine cellular sensitivity in air involved plating 10^3-10^4 cells (depending on cell line) into each well of a 96-well plate prior to drug exposure. Cells were than exposed to the Apaziquone (1nM-33mkM) continuously for 4 days at 37°C. Cells were then exposed to drug for 3 hat 37” in air or hypoxia, or in the presence of dicoumarol. The drug was then removed, 0.5 ml of fresh medium was added and the cells allowed to grow for 3 days. Subsequently, MTT was added and cells incubated for a further 4 h. After this time, culture medium and unconverted MTT were removed, the formazan crystals dissolved in DMSO and optical density measured on a multiwall spectrophotometer.
Name Type Language
Apaziquone hydroquinone
Common Name English
5-(1-Aziridinyl)-3-(hydroxymethyl)-2-[(1E)-3-hydroxy-1-propen-1-yl]-1-methyl-1H-indole-4,7-diol
Systematic Name English
1H-Indole-4,7-diol, 5-(1-aziridinyl)-3-(hydroxymethyl)-2-[(1E)-3-hydroxy-1-propen-1-yl]-1-methyl-
Systematic Name English
Apaziquone hydroquinone analog
Common Name English
Code System Code Type Description
PUBCHEM
445822
Created by admin on Fri Jul 07 00:56:17 UTC 2023 , Edited by admin on Fri Jul 07 00:56:17 UTC 2023
PRIMARY
CAS
1177895-58-7
Created by admin on Fri Jul 07 00:56:17 UTC 2023 , Edited by admin on Fri Jul 07 00:56:17 UTC 2023
PRIMARY
FDA UNII
TN4FH7XPZ8
Created by admin on Fri Jul 07 00:56:17 UTC 2023 , Edited by admin on Fri Jul 07 00:56:17 UTC 2023
PRIMARY