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Questions And Answer

• Pharmacological action

  Enzalutamide (XTANDI) is an oral androgen receptor antagonist, which is approved by the current clinical research and the US FDA (Food and Drug Administration), for the development of post-chemotherapy metastatic castration tolerance of prostate cancer Treatment (i.e. patients with prostate cancer after chemotherapy, cancer or cancer cells are still growing in such patients), can extend the survival of patients. The incidence of prostate cancer in the United States is very high, with an annual increase of nearly 240,000 patients (the highest among all cancers), nearly 30,000 deaths every year (second only to lung cancer, breast cancer, colorectal cancer),but its incidence is low in China.
  Enzalutamide is an androgen receptor inhibitor, the target of action is different from the approved cabbitaxel in 2010 and the approved abbitolone in 2011, and can competitively inhibit androgen and receptor binding, and can inhibition of androgen receptor nuclear transport and the interaction of the receptor and DNA. Vitro studies have shown that enzalutamide can inhibit prostate cancer cell proliferation and induce death, and enzalutamide reduces tumor volume in mouse prostate cancer xenograft model experiment. The main metabolite of enzalutamide is N-demethylol enamine, which shows similar inhibitory activity with enzalutamide in vitro. The recommended adult dose for the drug is daily 160mg, rapidly absorbed after medication, plasma concentrations to reach the highest level in 0.5~3h, the average terminal half-life is 5.8d, the main metabolic enzymes are CYP2C8 and CYP3A4. The drug should be avoided with strong CYP2C8 inhibitors (such as gemfibrozil), if it is needed for co-administration, should reduce the dose of enzalutamide to 80mg, 1 day.;

• Treatment

  In vitro, enzalutamide suppressed proliferation and induced apoptosis in human prostate cancer cell lines. The sensitivity of prostate cancer cells to T cell-mediated lysis via androgen receptor-dependent immunomodulation was enhanced by enzalutamide. Enzalutamide lacked androgen receptor agonist activity in CRPC cell models and induced tumour regression in CRPC xenograft models.

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• Indications

  For the treatment of metastatic or recurrence of advanced male castration tolerance of prostate cancer.;

• Clinical evaluation

  Enzalutamide is an oral androgen receptor inhibitor that reduces the risk of radiation-related disease progression and death.
  Although anti-androgen therapy has been the preferred treatment option for patients with metastatic prostate cancer for more than 70 years, researchers have found that male hormone receptors play an important role in the development of prostate cancer throughout the course of disease with the in-depth exploration of disease at the molecular level. FDA-approved new generation of androgen receptor antagonists such as abiraterone and enzolatamide have shown that it is benefit for patients with advanced prostate cancer after chemotherapy with docetaxel.
  Astellas in Japan and Johnson in the United States treat prostate cancer both through the target, according to statistics, similar to the treatment results, only a few differences, such as: abitron to be used simultaneously with steroid drugs , and enzalutamide is not required; abitron need to limit the diet, and enzalutamide does not need. Drugs in different countries is not the same as different the crowd, so there are price differences, but the effect is the same.
  This information was compiled by the Editor of the Chemicalbook (2015-09-20).;

• Side effects

  The main side effects of enxtran (XTANDI) are hypertension and fatigue. The most common adverse reactions (≥ 5%) are weakness/fatigue, back pain, diarrhea, joint pain, hot flashes, peripheral blood edema, musculoskeletal pain, headache, upper respiratory tract infection, muscle weakness, dizziness, insomnia, lower respiratory tract infection, spinal cord compression syndrome and cauda equina syndrome, hematuria, paresthesia, anxiety and hypertension.;

• Biological activity

  Enzalutamide (MDV3100) is an androgen receptor (AR) antagonist with an IC50 of 36 nM.
  Enzalutamide is an androgen receptor (AR) antagonist with an IC50 of 36 nM in vitro studies. In competitive experiments with 16β-[18F] fluoro-5α-DHT (18-FDHT), enzalutamide was found to have higher affinity for bilirubin than Bicalutamide when administered to AR. While enzalutamide had no effect on LNCaP/AR (AR-overexpression) of prostate cells. In parental LNCaP cells, Enzalutamide inhibits the production of prostate specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2), and inhibits their binding to the synthetic and rogen R1881. Enzalutamide inhibits the translation activity of the mutant AR protein (W741C, Trp at position 741 mutanting to Cys). MDV310 also blocked the nuclear translocation and coordination receptor complexes that recruit coactivators.;

• In vivo studies

  Enzalutamide treatment of castrated male mice carrying LNCa/AR xenografts, mice treated with 10 mg MDV310 per kilogram of body weight, can induce significant tumor regression.;

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