Developments in Nonsteroidal Antiandrogens Targeting the Androgen Receptor

@article{Liu2010DevelopmentsIN,
  title={Developments in Nonsteroidal Antiandrogens Targeting the Androgen Receptor},
  author={Bo Liu and Lei Su and Jingkun Geng and Junjie Liu and Guisen Zhao},
  journal={ChemMedChem},
  year={2010},
  volume={5}
}
The burden of prostate cancer (PCa) in the world is significant; PCa remains the most frequently diagnosed noncutaneous malignancy and remains the second leading cause of cancer-related deaths among men in Western countries. In 2009, approximately 192 280 men were diagnosed with PCa, and 27 360 men were estimated to die from the disease. The risk factor in PCa includes, but is not limited to, race, geography, age and gene rearrangements. Though patients with PCa initially respond to androgen… Expand
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References

SHOWING 1-10 OF 98 REFERENCES
Androgen receptor signaling in androgen-refractory prostate cancer.
TLDR
This review seeks to identify specific molecular events that may be linked directly to the progression to androgen-refractory prostate cancer and identifies mechanisms that appear to involve the androgen receptor (AR). Expand
Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer
TLDR
The diarylthiohydantoins RD162 and MDV3100 are characterized, two compounds optimized from a screen for nonsteroidal antiandrogens that retain activity in the setting of increased androgen receptor expression that appear to be promising candidates for treatment of advanced prostate cancer. Expand
Advances in Prostate Cancer Chemotherapy: A New Era Begins 1
  • K. Pienta, David C. Smith
  • Medicine
  • CA: a cancer journal for clinicians
  • 2005
TLDR
Two landmark studies demonstrated a survival advantage in androgen‐independent prostate cancer patients utilizing docetaxel chemotherapy, setting a new standard of care for this disease. Expand
Alterations of androgen receptor in prostate cancer
  • M. Linja, T. Visakorpi
  • Medicine, Biology
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2004
TLDR
It has now become clear that prostate carcinomas emerging during the androgen withdrawal therapy are capable of reactivating the AR-mediated signalling despite of the low levels of androgens. Expand
Discovery of BMS-641988, a novel and potent inhibitor of androgen receptor signaling for the treatment of prostate cancer.
TLDR
In mature rats, BMS-641988 strongly inhibited androgen-dependent growth of the ventral prostate and seminal vesicles and was highly efficacious in the LuCaP 23.1 human prostate xenograft model, inducing stasis throughout the approximately 30-day dosing. Expand
Targeting the androgen receptor pathway in prostate cancer.
TLDR
A number of novel agents targeting the AR signaling pathway are being developed, including more effective antiandrogens, inhibitors of CYP17, an enzyme required for androgen synthesis, inhibitor of 5alpha-reductase, and inhibitors of HSP90 which protects AR from degradation. Expand
Molecular mechanisms of castration-resistant prostate cancer progression.
TLDR
Research data show many different processes to be involved in the acquisition of hormone resistance, and one observes interdependence between these processes, indicating a complex network at play in the development of hormones resistance. Expand
Mechanisms mediating androgen receptor reactivation after castration.
TLDR
Significantly, the androgen receptor (AR) is expressed at high levels in most cases of CRPC, and these tumors resume their expression of multiple AR-regulated genes, indicating that AR transcriptional activity becomes reactivated at this stage of the disease. Expand
Structural basis for antagonism and resistance of bicalutamide in prostate cancer
TLDR
The three-dimensional structure demonstrates that the B ring of R-bicalutamide in the W741L mutant is accommodated at the location of the indole ring of Trp-741 in the WT AR bound to dihydrotestosterone. Expand
Discovery and mechanistic characterization of a novel selective nuclear androgen receptor exporter for the treatment of prostate cancer.
TLDR
SNARE-1 inhibits AR function by a mechanism that is distinct from clinically available antiandrogens, such that it might inform novel methods to block AR function in androgen-independent prostate cancer. Expand
...
1
2
3
4
5
...