929029-32-3Relevant academic research and scientific papers
ANDROGEN RECEPTOR PROTEIN DEGRADERS
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Paragraph 0178; 0262, (2020/07/21)
The present disclosure provides compounds represented by Formula (I): A—L—B (I), and the salts or solvates thereof, wherein A, L, and B are as defined in the specification. Compounds having Formula (I) are androgen receptor degraders useful for the treatment of cancer.
Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer
Han, Xin,Wang, Chao,Qin, Chong,Xiang, Weiguo,Fernandez-Salas, Ester,Yang, Chao-Yie,Wang, Mi,Zhao, Lijie,Xu, Tianfeng,Chinnaswamy, Krishnapriya,Delproposto, James,Stuckey, Jeanne,Wang, Shaomeng
, p. 941 - 964 (2019/01/21)
We report herein the discovery of highly potent PROTAC degraders of androgen receptor (AR), as exemplified by compound 34 (ARD-69). ARD-69 induces degradation of AR protein in AR-positive prostate cancer cell lines in a dose- and time-dependent manner. ARD-69 achieves DC50 values of 0.86, 0.76, and 10.4 nM in LNCaP, VCaP, and 22Rv1 AR+ prostate cancer cell lines, respectively. ARD-69 is capable of reducing the AR protein level by >95% in these prostate cancer cell lines and effectively suppressing AR-regulated gene expression. ARD-69 potently inhibits cell growth in these AR-positive prostate cancer cell lines and is >100 times more potent than AR antagonists. A single dose of ARD-69 effectively reduces the level of AR protein in xenograft tumor tissue in mice. Further optimization of ARD-69 may ultimately lead to a new therapy for AR+, castration-resistant prostate cancer.
METHODS OF TREATING ADVANCED PROSTATE CANCER
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Paragraph 0015; 0126, (2018/11/21)
Provided herein are methods for treating metastatic prostate cancer using anti-androgen compounds and radionuclide-labeled androgens.
Synthesis and biological evaluation of [18F]bicalutamide, 4-[76Br]bromobicalutamide, and 4-[76Br]bromo- thiobicalutamide as non-steroidal androgens for prostate cancer imaging
Parent, Ephraim E.,Dence, Carmen S.,Jenks, Carl,Sharp, Terry L.,Welch, Michael J.,Katzenellenbogen, John A.
, p. 1028 - 1040 (2008/02/01)
Androgen receptors (AR) are overexpressed in most primary and metastatic prostate cancers. To develop a nonsteroidal AR-mediated imaging agent, we synthesized and radiolabeled several analogs of the potent antiandrogen bicalutamide: [18F]bicalutamide, 4-[76Br] bromobicalutamide, and [76Br]bromo-thiobicalutamide. Two of these analogs, 4-[76Br]bromobicalutamide and [76Br]bromo- thiobicalutamide, were found to have a substantially increased affinity for the androgen receptor (AR) compared to that of bicalutamide. The synthesis of [ 18F]bicalutamide utilized a pseudocarrier approach to effect addition of a carbanion generated from tracer-level amounts of a radiolabeled precursor to an unlabeled carbonyl precursor. 4-[76Br]Bromobicalutamide and [76Br]bromo-thiobicalutamide were labeled through electrophilic bromination of a tributylstannane precursor. The former could be prepared in high specific activity, and its tissue distribution was tested in vivo. Androgen target tissue uptake was evident in castrated adult male rats; however, in DES-treated, AR-positive, tumor-bearing male mice, tumor uptake was low.
