Evidence map›Paper›PMID 37516113›Full record

ArticleCell chemical biology2023

Paralog-dependent isogenic cell assay cascade generates highly selective SLC16A3 inhibitors.

Vojtech Dvorak, Andrea Casiraghi, Claire Colas, Anna Koren, Tatjana Tomek, Fabian Offensperger, Andrea Rukavina, Gary Tin, Elisa Hahn, Sarah Dobner and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

18 authors at 3 institutions in 1 country.

Vojtech DvorakCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Andrea CasiraghiCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Claire ColasDepartment of Pharmaceutical Sciences, University of Vienna, 1090 Vienna, Austria.
Anna KorenCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Tatjana TomekCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Fabian OffenspergerCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Andrea RukavinaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Gary TinCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Elisa HahnCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Sarah DobnerCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Fabian FrommeltCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Andras BoeszoermenyiCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Viktoriia BernadaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
J Thomas HannichCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Gerhard F EckerDepartment of Pharmaceutical Sciences, University of Vienna, 1090 Vienna, Austria.
Georg E WinterCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Stefan KubicekCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Giulio Superti-FurgaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: GSuperti@cemm.oeaw.ac.at.
Austrian Academy of Sciences · ATCeMM Research Center for Molecular Medicine · ATUniversity of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite being considered druggable and attractive therapeutic targets, most of the solute carrier (SLC) membrane transporters remain pharmacologically underexploited. One of the reasons for this is a lack of reliable chemical screening assays, made difficult by functional redundancies among SLCs. In this study we leveraged synthetic lethality between the lactate transporters SLC16A1 and SLC16A3 in a screening strategy that we call paralog-dependent isogenic cell assay (PARADISO). The system involves five isogenic cell lines, each dependent on various paralog genes for survival/fitness, arranged in a screening cascade tuned for the identification of SLC16A3 inhibitors. We screened a diversity-oriented library of ∼90,000 compounds and further developed our hits into slCeMM1, a paralog-selective and potent SLC16A3 inhibitor. By implementing chemoproteomics, we showed that slCeMM1 is selective also at the proteome-wide level, thus fulfilling an important criterion for chemical probes. This study represents a framework for the development of specific cell-based drug discovery assays.

Indexed as

Carrier ProteinsDrug DiscoveryMembrane Transport ProteinsCarrier ProteinsMembrane Transport ProteinsCell-based AssayChemical ProbeChemical ProteomicsChemical ScreeningMCT4SLCSLC16SLC16A3Solute Carrier Transporters

Identifiers

PMID37516113
PMCPMC10437005
OpenAlexW4385351603

What OpenQuestion holds

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LicenceCC BY
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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.