Evidence map›Paper›PMID 36656639›Full record

ArticleeLife2023

Selective androgen receptor degrader (SARD) to overcome antiandrogen resistance in castration-resistant prostate cancer.

Meng Wu, Rongyu Zhang, Zixiong Zhang, Ning Zhang, Chenfan Li, Yongli Xie, Haoran Xia, Fangjiao Huang, Ruoying Zhang, Ming Liu and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Androgen Receptor in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2023
    Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Meng Wu *Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.ORCID 0000-0001-7381-5591
Rongyu Zhang *Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua, China.ORCID 0000-0001-7361-9152
Zixiong Zhang *Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
Ning ZhangInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
Chenfan LiKey Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua, China.
Yongli XieInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
Haoran XiaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Fangjiao HuangKey Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua, China.
Ruoying ZhangKey Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua, China.
Ming LiuDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Xiaoyu LiInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
Shan CenInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
Jinming ZhouInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.ORCID 0000-0003-1610-5061
Academy of Medical Sciences · GBZhejiang Normal University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In patients with castration-resistant prostate cancer (CRPC), clinical resistances such as androgen receptor (AR) mutation, AR overexpression, and AR splice variants (ARVs) limit the effectiveness of second-generation antiandrogens (SGAs). Several strategies have been implemented to develop novel antiandrogens to circumvent the occurring resistance. Here, we found and identified a bifunctional small molecule Z15, which is both an effective AR antagonist and a selective AR degrader. Z15 could directly interact with the ligand-binding domain (LBD) and activation function-1 region of AR, and promote AR degradation through the proteasome pathway. In vitro and in vivo studies showed that Z15 efficiently suppressed AR, AR mutants and ARVs transcription activity, downregulated mRNA and protein levels of AR downstream target genes, thereby overcoming AR LBD mutations, AR amplification, and ARVs-induced SGAs resistance in CRPC. In conclusion, our data illustrate the synergistic importance of AR antagonism and degradation in advanced prostate cancer treatment.

Indexed as

Prostatic Neoplasms, Castration-ResistantReceptors, AndrogenAndrogen AntagonistsAndrogen Receptor AntagonistsCell Line, TumorDrug Resistance, NeoplasmHumansMaleNitrilesSignal TransductionAndrogen AntagonistsAndrogen Receptor AntagonistsNitrilesReceptors, Androgenandrogen receptorantiandrogencancer biologycastration-resistant prostate cancerdegraderenzalutamide resistancehuman

Identifiers

PMID36656639
PMCPMC9901937
OpenAlexW4317434392

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.