Evidence map›Paper›PMID 41553426›Full record

ArticleEuropean biophysics journal : EBJ2026

Achieving femtomolar affinities in structure-based drug design.

Asta Zubrienė, Maija Kurtenoka, Vaida Paketurytė-Latvė, Janis Leitans, Elena Manakova, Mantas Žvirblis, Andris Kazaks, Vladislava Eimonta, Kaspars Tars, Saulius Gražulis and 5 more

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Article in European biophysics journal : EBJ, 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
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Asta ZubrienėDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Maija KurtenokaDepartment of Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia.
Vaida Paketurytė-LatvėDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Janis LeitansLatvian Biomedical Research and Study Centre, Ratsupites 1 k-1, Riga, 1067, Latvia.
Elena ManakovaDepartment of Protein-DNA Interactions, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Mantas ŽvirblisDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Andris KazaksLatvian Biomedical Research and Study Centre, Ratsupites 1 k-1, Riga, 1067, Latvia.
Vladislava EimontaLatvian Biomedical Research and Study Centre, Ratsupites 1 k-1, Riga, 1067, Latvia.
Kaspars TarsLatvian Biomedical Research and Study Centre, Ratsupites 1 k-1, Riga, 1067, Latvia.
Saulius GražulisSector of Crystallography and Chemical Informatics, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Vytautas PetrauskasDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Jurgita MatulienėDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Virginija DudutienėDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania.
Kirill ShubinDepartment of Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia. kir101@osi.lv.
Daumantas MatulisDepartment of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, Vilnius, LT-10257, Lithuania. daumantas.matulis@bti.vu.lt.ORCID http://orcid.org/0000-0002-6178-6276

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Developing small-molecule compounds as effective and safe pharmaceuticals relies on their ability to bind disease-associated proteins with high affinity and selectivity. However, achieving ultra-high affinity in the femtomolar range is a major challenge in medicinal chemistry due to the inherent constraints of protein-ligand interactions. Here, we introduce a novel class of di-meta-substituted fluorinated benzenesulfonamide compounds that achieve an extraordinary dissociation constant of 44 fM for carbonic anhydrase IX (CAIX). CAIX, a transmembrane enzyme implicated in hypoxic tumor progression through the increase of microenvironment acidity, represents a promising target for anticancer therapy. Inhibiting CAIX may help suppress tumor growth and improve cancer treatment outcomes. The newly developed compounds exhibit the highest affinity for CAIX reported to date and rank among the strongest known non-covalent small-molecule inhibitors.

Indexed as

Carbonic Anhydrase InhibitorsCarbonic Anhydrase IXDrug DesignSulfonamidesBenzenesulfonamidesHumansLigandsProtein BindingBenzenesulfonamidesCarbonic Anhydrase InhibitorsCarbonic Anhydrase IXLigandsSulfonamidesBinding affinityCarbonic anhydrase IXDrug discoveryProtein-ligand bindingStructural biology

Identifiers

PMID41553426

What OpenQuestion holds

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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.