ArticleActa crystallographica. Section D, Biological crystallography2014
Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules.
Article in Acta crystallographica. Section D, Biological crystallography, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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.
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.
Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia.Nature communications · 2023Article
- Dual protein kinase and nucleoside kinase modulators for rationally designed polypharmacology.Nature communications · 2017Article
- Human Biodistribution and Radiation Dosimetry ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017Article
- Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features.Science advances · 2016Article
- Structure-guided development of deoxycytidine kinase inhibitors with nanomolar affinity and improved metabolic stability.Journal of medicinal chemistry · 2014Article
- Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication.The Journal of experimental medicine · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Deoxycytidine kinase (dCK) is a key enzyme in the nucleoside salvage pathway that is also required for the activation of several anticancer and antiviral nucleoside analog prodrugs. Additionally, dCK has been implicated in immune disorders and has been found to be overexpressed in several cancers. To allow the probing and modulation of dCK activity, a new class of small-molecule inhibitors of the enzyme were developed. Here, the structural characterization of four of these inhibitors in complex with human dCK is presented. The structures reveal that the compounds occupy the nucleoside-binding site and bind to the open form of dCK. Surprisingly, a slight variation in the nature of the substituent at the 5-position of the thiazole ring governs whether the active site of the enzyme is occupied by one or two inhibitor molecules. Moreover, this substituent plays a critical role in determining the affinity, improving it from >700 to 1.5 nM in the best binder. These structures lay the groundwork for future modifications that would result in even tighter binding and the correct placement of moieties that confer favorable pharmacodynamics and pharmacokinetic properties.
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Registered trials
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