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… Expand
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. Expand
Design, synthesis, and biological evaluation of small molecule PROTACs for potential anticancer effects
Androgen receptor (AR) reactivation was closely related with the recurrence of human prostate cancer. Currently, several limitations of AR inhibitors impede their application, such as the acquiredExpand
Methoxychalcone inhibitors of androgen receptor translocation and function.
Methoxychalcones are reported that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non-responsive state, thus demonstrating a novel chemical scaffold for anti androgen development and a unique mechanism of antiandrogen activity. Expand
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. Expand
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. Expand
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. Expand
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. Expand
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. Expand
Synthesis, characterization and reactivity study of aluminum compounds incorporating bi- and tri-dentate pyrrole–piperazine ligands
Substituted bi- and tri-dentate pyrrole–piperazine precursors, C4H3NH-[2-CH2N(CH2CH2)2NPh] (1) and C4H2NH-{2,5-[CH2N(CH2CH2)2NPh]2} (2) are synthesized and the corresponding Al derivatives areExpand
Asymmetric Michael additions of α-cyanoacetates by soft Lewis acid/hard Brønsted acid catalysis: stereodivergency with bi- vs. monometallic catalysts
The direct asymmetric conjugate addition of α-cyanoacetates to enones generating densely functionalized α-amino acid precursors with adjacent quaternary and tertiary stereocenters is describedExpand


Androgen receptor signaling in androgen-refractory prostate cancer.
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
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
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
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.
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.
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.
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.
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
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.
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