Evidence map›Paper›PMID 39800739›Full record

ArticleCell death discovery2025

Developing novel Lin28 inhibitors by computer aided drug design.

Victor M Matias-Barrios, Mariia Radaeva, Graciella Rosellinny, Qiongqiong Jia, Ning Xie, Monica Villanueva, Hanadi Ibrahim, Jason Smith, Martin Gleave, Nada Lallous and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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.

Victor M Matias-Barrios *The Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.ORCID http://orcid.org/0000-0002-1244-6128
Mariia Radaeva *The Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Graciella RosellinnyThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Qiongqiong JiaThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Ning XieThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Monica VillanuevaDepartment of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.
Hanadi IbrahimThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Jason SmithThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Martin GleaveThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.ORCID http://orcid.org/0000-0003-4235-0167
Nada LallousThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.ORCID http://orcid.org/0000-0002-8665-8641
Suzana K StrausDepartment of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.
Artem CherkasovThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.ORCID http://orcid.org/0000-0002-1599-1439
Xuesen DongThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada. xdong@prostatecentre.com.ORCID http://orcid.org/0000-0002-3115-3371

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT156150, PTJ178063, PJT-196012U.S. Department of Defense (United States Department of Defense) W81XWH2010581
6 · The paper itself

Abstract

Lin28 is a key regulator of cancer stem cell gene network that promotes therapy-resistant tumor progression in various tumors. However, no Lin28 inhibitor has been approved to treat cancer patients, urging exploration of novel compounds as candidates to be tested for clinical trials. In this contribution, we applied computer-aided drug design (CADD) in combination with quantitative biochemical and biological assays. These efforts led to the discovery of Ln268 as a drug candidate that can block Lin28 from binding to its RNA substrates and inhibit Lin28 activities. Ln268 suppressed Lin28-mediated cancer cell proliferation and spheroid growth. Results from nuclear magnetic resonance spectroscopy confirmed that Ln268 perturbs the conformation of the zinc knuckle domain of Lin28, validating the rational drug design by CADD. The inhibitory effects of Ln268 are dependent on Lin28 protein expression in cancer cells, highlighting limited off-target effects of Ln268. Moreover, Ln268 synergizes with several chemotherapy drugs to suppress tumor cell growth. In summary, Ln268 is a promising candidate for further development to target Lin28 as a cancer therapy.

Identifiers

PMID39800739
PMCPMC11725581

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Registered trials

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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.