Evidence map›Paper›PMID 42089431›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Molecular Glue cc-885 Inhibits VHL-Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation.

Taowei Yang, Qihao Li, Kun Ye, Kezhi Liu, Mi Zhou, Minyu Chen, Lican Liao, Kangbo Huang, Zhu Wang, Qiong Deng and 6 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Taowei YangDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.ORCID https://orcid.org/0000-0002-1827-2552
Qihao LiDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Kun YeDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Kezhi LiuDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Mi ZhouDepartment of Oncology and Southwest Cancer Center, Southwest Hospital of Third Military Medical University (Army Medical University), Chongqing, China.
Minyu ChenDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Lican LiaoDepartment of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Kangbo HuangDepartment of Urology, Sun Yat-sen University Cancer center, Guangzhou, Guangdong, China.
Zhu WangDepartment of Urology, The People's Hospital of Longhua, Shenzhen, Guangdong, China.
Qiong DengDepartment of Urology, The People's Hospital of Longhua, Shenzhen, Guangdong, China.
Jieyan WangDepartment of Urology, The People's Hospital of Longhua, Shenzhen, Guangdong, China.
Meiyu JinDepartment of Urology, The People's Hospital of Longhua, Shenzhen, Guangdong, China.
Xu ChenDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Hui LiangDepartment of Urology, The People's Hospital of Longhua, Shenzhen, Guangdong, China.
Jiaxing ZhangDepartment of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.ORCID https://orcid.org/0000-0003-3200-173X
Junhang LuoDepartment of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.ORCID https://orcid.org/0000-0002-5706-0990

Funding

National Natural Science Foundation of China 82373433National Natural Science Foundation of China 82403968National Natural Science Foundation of China 82473160Natural Science Foundation of Guangdong Province 2025A1515010988
6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive form of kidney cancer with VHL mutations present in > 50% of cases. These mutations lead to dysregulation of hypoxia-inducible factors (HIFs) and activation of oncogenic pathways, making VHL-deficient ccRCC a challenging target for therapy. In this study, we identified cc-885, a molecular glue degrader, as a selective inhibitor of VHL-deficient ccRCC. cc-885 promotes ubiquitination and degradation of transcription factor ETS1, which cooperates with EPAS1 (HIF-2α) to drive tumorigenesis. We demonstrated that cc-885 selectively targeted the p51 and p42 isoforms of ETS1, disrupting p27/p51 balance and suppressing ETS1 transcriptional activity. Moreover, combining cc-885 with an EPAS1 inhibitor, belzutifan, significantly enhanced the anti-tumor efficacy. Our findings provide a novel and precise therapeutic strategy for VHL-deficient ccRCC by targeting ETS1 degradation and disrupting the ETS1-EPAS1 complex.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsProto-Oncogene Protein c-ets-1Von Hippel-Lindau Tumor Suppressor ProteinAnimalsCell Line, TumorHumansMiceProteolysisUbiquitinationETS1 protein, humanProto-Oncogene Protein c-ets-1VHL protein, humanVon Hippel-Lindau Tumor Suppressor Proteinmolecular cancermolecular dynamics simulationrenal cell carcinomaubiquitination

Identifiers

PMID42089431
PMCPMC13335456

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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.