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
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+
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22509926Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22509926
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11497261 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Curative | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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: |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02563561
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7946565
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.
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1177895-58-7
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TN4FH7XPZ8
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ACTIVE MOIETY
PRODRUG (METABOLITE ACTIVE)