Apaziquone

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Apaziquone
Apaziquone.svg
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • (E)-5-(1-Azirinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-1H-indole-4,7-dione
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C15H16N2O4
Molar mass 288.303 g·mol−1
3D model (JSmol)
  • Cn1c(c(c2c1C(=O)C=C(C2=O)N3CC3)CO)/C=C/CO
  • InChI=1S/C15H16N2O4/c1-16-10(3-2-6-18)9(8-19)13-14(16)12(20)7-11(15(13)21)17-4-5-17/h2-3,7,18-19H,4-6,8H2,1H3/b3-2+ Yes check.svgY
  • Key:MXPOCMVWFLDDLZ-NSCUHMNNSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Apaziquone (tentative trade name EOquin) [1] is an indolequinone that is a bioreductive prodrug similar to 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. The active metabolites alkylate DNA and lead to apoptosis. [2] This activity is preferentially expressed in neoplastic cells.

After administration of apaziquone directly into the urinary bladder (intravesically), the drug and its active metabolite were not detected in plasma, and there were no systemic side effects. [3] [4]

Apaziquone has been applied in clinical studies sponsored by Spectrum Pharmaceuticals and Allergan for the treatment of superficial (non-muscle invasive) bladder cancer. [3] 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 (FDA) has granted Fast Track review status to apaziquone for this indication. [5]

Related Research Articles

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Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. It is the urologic chronic pelvic pain syndrome of women. Symptoms include feeling the need to urinate right away, needing to urinate often, and pain with sex. IC/BPS is associated with depression and lower quality of life. Many of those affected also have irritable bowel syndrome and fibromyalgia.

<span class="mw-page-title-main">Prostate</span> Gland of the male reproductive system

The prostate is an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemically, and physiologically. Anatomically, the prostate is found below the bladder, with the urethra passing through it. It is described in gross anatomy as consisting of lobes and in microanatomy by zone. It is surrounded by an elastic, fibromuscular capsule and contains glandular tissue, as well as connective tissue.

<span class="mw-page-title-main">Cystoscopy</span> Medical procedure; endoscopy of the urinary bladder via the urethra

Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.

<span class="mw-page-title-main">Bladder cancer</span> Urinary system cancer that begins in the urinary bladder

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 malignant.

<span class="mw-page-title-main">Prostatectomy</span> Surgical removal of all or part of the prostate gland

Prostatectomy is the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prostate cancer and for other cancers of the pelvis.

<span class="mw-page-title-main">Tamsulosin</span> Medication

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Oxybutynin, sold under the brand name Ditropan among others, is an anticholinergic medication primarily used to treat overactive bladder. It is widely considered a first-line therapy for overactive bladder due to its well-studied side effect profile, broad applicability, and continued efficacy over long periods of time. It works similar to tolterodine, darifenacin, and solifenacin, although it is usually preferred over these medications. It is sometimes used off-label for treatment of hyperhidrosis, or excessive sweating. It has also been used off-label to treat bedwetting in children, but this use has declined, as it is most likely ineffective in this role. It is taken by mouth or applied to the skin.

<span class="mw-page-title-main">Transitional cell carcinoma</span> Medical condition

Transitional cell carcinoma is a type of cancer that arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs. It typically occurs in the urothelium of the urinary system; in that case, it is also called urothelial carcinoma. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. Symptoms of urothelial carcinoma in the bladder include hematuria. Diagnosis includes urine analysis and imaging of the urinary tract (cystoscopy).

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<span class="mw-page-title-main">Chronic prostatitis/chronic pelvic pain syndrome</span> Medical condition

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<span class="mw-page-title-main">Urodynamic testing</span> Assessment of bladder and urethra performance

Urodynamic testing or urodynamics is a study that assesses how the bladder and urethra are performing their job of storing and releasing urine. Urodynamic tests can help explain symptoms such as:

<span class="mw-page-title-main">Chlornaphazine</span> Chemical compound

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<span class="mw-page-title-main">Eosinophilic cystitis</span> Medical condition

Eosinophilic cystitis is a rare type of interstitial cystitis first reported in 1960 by Edwin Brown. Eosinophilic cystitis has been linked to a number of etiological factors, including allergies, bladder tumors, trauma to the bladder, parasitic infections, and chemotherapy drugs, though the exact cause of the condition is still unknown. The antigen-antibody response is most likely the cause of eosinophilic cystitis. This results in the generation of different immunoglobulins, which activate eosinophils and start the inflammatory process.

<span class="mw-page-title-main">Invasive urothelial carcinoma</span> Medical condition

Invasive urothelial carcinoma is a type of transitional cell carcinoma. It is a type of cancer that develops in the urinary system: the kidney, urinary bladder, and accessory organs. Transitional cell carcinoma is the most common type of bladder cancer and cancer of the ureter, urethra, renal pelvis, the ureters, the bladder, and parts of the urethra and urachus. It originates from tissue lining the inner surface of these hollow organs - transitional epithelium. The invading tumors can extend from the kidney collecting system to the bladder.

<span class="mw-page-title-main">Vibegron</span> Medication

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<span class="mw-page-title-main">Intravesical drug delivery</span> Intravesical drug delivery, drug delivery to the bladder

Intravesical drug delivery is the delivery of medications directly into the bladder by urinary catheter. This method of drug delivery is used to directly target diseases of the bladder such as interstitial cystitis and bladder cancer, but currently faces obstacles such as low drug retention time due to washing out with urine and issues with the low permeability of the bladder wall itself. Due to the advantages of directly targeting the bladder, as well as the effectiveness of permeability enhancers, advances in intravesical drug carriers, and mucoadhesive, intravesical drug delivery is becoming more effective and of increased interest in the medical community.

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References

  1. "UvA researcher develops new bladder cancer medication". University of Amsterdam. 25 Jul 2007. Archived from the original on 2011-07-16.
  2. NCI. "apaziquone". Archived from the original on 9 May 2009. Retrieved 2009-06-07.
  3. 1 2 Puri R, Palit V, Loadman PM, et al. (October 2006). "Phase I/II pilot study of intravesical apaziquone (EO9) for superficial bladder cancer". J. Urol. 176 (4 Pt 1): 1344–8. arXiv: 1506.05421 . doi:10.1016/j.juro.2006.06.047. PMID   16952628.
  4. Hendricksen K, Gleason D, Young JM, et al. (July 2008). "Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer". J. Urol. 180 (1): 116–20. doi:10.1016/j.juro.2008.03.031. PMID   18485407.
  5. "FDA Designates Fast Track Status For Apaziquone (EOquin) For Bladder Cancer". Medical News Today. 22 Jul 2009.