Apaziquone (tentative trade name EOquin) is an indolequinone that is a bioreductive

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

similar to the older

chemotherapeutic agent This is a list of chemotherapeutic agents, also known as cytotoxic agents or cytostatic drugs, that are known to be of use in chemotherapy for cancer. This list is organized by type of agent, although the subsections are not necessarily definitive ...

mitomycin C Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity. Medical uses It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancers, and breast c ...

. In

hypoxic Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

cells, such as those on the inner surface of the

urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...

, apaziquone is converted to active metabolites by intracellular

reductase A reductase is an enzyme that catalyzes a reduction reaction. Examples * 5α-Reductase * 5β-Reductase * Dihydrofolate reductase * HMG-CoA reductase * Methemoglobin reductase * Ribonucleotide reductase * Thioredoxin reductase * ''E. coli'' ...

s. The active metabolites

alkylate An alkylation unit (alky) is one of the conversion processes used in petroleum refineries. It is used to convert isobutane and low-molecular-weight alkenes (primarily a mixture of propene and butene) into alkylate, a high octane gasoline component ...

DNA and lead to

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. This activity is preferentially expressed in

neoplastic cells A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

. After administration of apaziquone directly into the urinary bladder (intravesically), the drug and its active metabolite were not detected in

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

, and there were no systemic

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, consequence ...

s. Apaziquone has been applied in clinical studies sponsored by Spectrum Pharmaceuticals and

Allergan Allergan plc is an American, Irish-domiciled pharmaceutical company that acquires, develops, manufactures and markets brand name drugs and medical devices in the areas of medical aesthetics, eye care, central nervous system, and gastroenterology. ...

for the treatment of superficial (non-muscle invasive)

bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...

. 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 U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) has granted

Fast Track The fast track is an informal English term meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement". By definition, it implies that a less direct, slower route also exists. Fast track or F ...

review status to apaziquone for this indication.

References

{{reflist Primary alcohols Antineoplastic drugs Aziridines Indolequinones