Developments in Nonsteroidal Antiandrogens Targeting the Androgen Receptor

  title={Developments in Nonsteroidal Antiandrogens Targeting the Androgen Receptor},
  author={Bo Liu and Lei Su and Jingkun Geng and Junjie Liu and Guisen Zhao},
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… 

Recent Developments in Androgen Receptor Antagonists

This review summarizes the preclinical development of androgen receptor antagonists, conventional androgens receptor antagonists that competitively bind to the ligand binding domain of the androgen receptors and coactivator antagonists of theandrogen receptor, including both activation function‐2 antagonists and binding function‐3 antagonists.

Design, synthesis, and biological evaluation of small molecule PROTACs for potential anticancer effects

The results suggested that PAP508 is a potent and efficacious compound for the development of PROTAC targeted AR, and can inhibit the proliferation, migration, and invasion of prostate cancer cells.

Methoxychalcone inhibitors of androgen receptor translocation and function.

Sebaceous carcinoma of the eyelid.

Clinical relevant topics regarding SC are focused on the cellular mechanisms regarding the etiology of SC, signaling pathways involved in the pathogenesis, and how miRNAs interact with these cascades.

Interaction mechanism exploration of R-bicalutamide/S-1 with WT/W741L AR using molecular dynamics simulations.

The obtained results indicate that M895 and W741 are vital amino acids in the antagonism of R-bicalutamide, and H12 tends to cover the AR ligand-binding domain to a certain degree, changing the androgen receptor from an antagonistic to an agonistic conformation.

Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)

A number of analogs of aryl hydantoin 1 are described designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand–androgen receptor interactions.

One-Pot Multicomponent Synthesis of Methoxybenzo[h]quinoline-3-carbonitrile Derivatives; Anti-Chagas, X-ray, and In Silico ADME/Tox Profiling Studies

Several methoxybenzo[h]quinoline-3-carbonitrile analogs were designed and synthesized in a repositioning approach to developing compounds with anti-prostate cancer and anti-Chagas disease properties.

Overexpression of HepaCAM inhibits cell viability and motility through suppressing nucleus translocation of androgen receptor and ERK signaling in prostate cancer

HepaCAM is suppressed in a variety of human cancers, and involved in cell adhesion, growth, migration, invasion, and survival, but the expression and function in prostate cancer are still unknown.

Design, Synthesis, and Evaluation of Aryl Hydantoins and Ureas as Antischistosomal Agents

This document summarizes current capabilities, research and operational priorities, and plans for further studies that were established at the 2015 USGS workshop on quantitative hazard assessments of earthquake-triggered landsliding and liquefaction in the Central American region.



Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer

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.

Advances in Prostate Cancer Chemotherapy: A New Era Begins 1

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.

Alterations of androgen receptor in prostate cancer

  • M. LinjaT. Visakorpi
  • Biology, Medicine
    The Journal of Steroid Biochemistry and Molecular Biology
  • 2004

Discovery of BMS-641988, a novel and potent inhibitor of androgen receptor signaling for the treatment of prostate cancer.

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.

Targeting the androgen receptor pathway in prostate cancer.

Molecular mechanisms of castration-resistant prostate cancer progression.

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.

Structural basis for antagonism and resistance of bicalutamide in prostate cancer

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.

Discovery and mechanistic characterization of a novel selective nuclear androgen receptor exporter for the treatment of prostate cancer.

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.

Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth.

Maximal therapeutic efficacy in the treatment of castration-resistant prostate cancer will require novel agents capable of inhibiting intracrine steroidogenic pathways within the prostate tumor microenvironment.