Apaziquone
Encyclopedia
Apaziquone 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 reductase
s. The active metabolites alkylate DNA and lead to apoptotic cell death
. This activity is preferentially expressed in neoplastic cells.
After administration of apaziquone directly into the urinary bladder, the drug and its active metabolite were not detected in plasma
, and there were no systemic side effect
s
Apaziquone has been applied in clinical studies sponsored by Spectrum Pharmaceuticals
and Allergan, Inc. for the treatment of superficial (non-muscle invasive) bladder cancer. Approximately 70% of all newly diagnosed patients with bladder cancer have non-muscle invasive bladder cancer and over one million patients in the United States and Europe are affected by the disease. The US Food and Drug Administration (FDA) has granted Fast Track review status to apaziquone for this indication.
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
and a chemical analog of the older chemotherapeutic agent
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
mitomycin C. In hypoxic cells
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
, such as those on the inner surface of the urinary bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
, apaziquone is converted to active metabolites by intracellular reductase
Reductase
-Examples:* 5-alpha reductase* Dihydrofolate reductase* HMG-CoA reductase* Methemoglobin reductase* Ribonucleotide reductase* Thioredoxin reductase* E. coli nitroreductase* Methylenetetrahydrofolate reductase...
s. The active metabolites alkylate DNA and lead to apoptotic cell death
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. This activity is preferentially expressed in neoplastic cells.
After administration of apaziquone directly into the urinary bladder, the drug and its active metabolite were not detected in plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, and there were no systemic side effect
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.Occasionally, drugs are...
s
Apaziquone has been applied in clinical studies sponsored by Spectrum Pharmaceuticals
Spectrum Pharmaceuticals
Spectrum Pharmaceuticals is an American biopharmaceutical company. The company is located in Irvine, California.-Approved drugs:In the US, Spectrum markets Fusilev and Zevalin.Fusilev for injection is a drug that was approved by the U.S...
and Allergan, Inc. for the treatment of superficial (non-muscle invasive) bladder cancer. Approximately 70% of all newly diagnosed patients with bladder cancer have non-muscle invasive bladder cancer and over one million patients in the United States and Europe are affected by the disease. The US Food and Drug Administration (FDA) has granted Fast Track review status to apaziquone for this indication.