Evidence map›Paper›PMID 38698214›Full record

ArticleActa pharmacologica Sinica2024

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

Xi-Shan Wu, Xiao-Yu Luo, Cheng-Chang Li, Xiao-Fan Zhao, Cheng Zhang, Xiao-Shan Chen, Zhi-Fang Lu, Tong Wu, Hao-Nan Yu, Chao Peng and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

14 authors.

Xi-Shan Wu *State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China. wu_xishan@gibh.ac.cn.
Xiao-Yu Luo *State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Cheng-Chang LiState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Xiao-Fan ZhaoGMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
Cheng ZhangState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Xiao-Shan ChenState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Zhi-Fang LuState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Tong WuState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Hao-Nan YuState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Chao PengJiangsu S&T Exchange Center with Foreign Countries, No. 175 Longpan Road, Nanjing, 210042, China.
Qing-Qing HuState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Hui ShenState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China.
Yong XuState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China. xu_yong@gibh.ac.cn.
Yan ZhangState Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou, 510530 China; Guangzhou Medical University, Guangzhou, 511436, China. zhang_yan2012@gibh.ac.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Indexed as

Antineoplastic AgentsCell ProliferationNuclear Receptor Subfamily 1, Group F, Member 3Prostatic NeoplasmsQuinolinesAnimalsCell Line, TumorDrug DiscoveryDrug Inverse AgonismHumansMaleMiceMice, Inbred BALB CMice, NudeStructure-Activity RelationshipXenograft Model Antitumor Assays1,2,3,4-tetrahydroquinolineAntineoplastic AgentsNuclear Receptor Subfamily 1, Group F, Member 3Quinolines1,2,3,4-tetrahydroquinoline derivativesinverse agonistsprostate cancerRORγ

Identifiers

PMID38698214
PMCPMC11336105

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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.