ArticleJournal of medicinal chemistry2014
Structure-guided development of deoxycytidine kinase inhibitors with nanomolar affinity and improved metabolic stability.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 16 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
- Review
- STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Development and preclinical pharmacology of a novel dCK inhibitor, DI-87.Biochemical pharmacology · 2020Article
- ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways.Nature communications · 2017Article
- Human Biodistribution and Radiation Dosimetry ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017Article
- [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil.Nature communications · 2016Article
- Potential Deoxycytidine Kinase Inhibitory Activity of Amaryllidaceae Alkaloids: AnJournal of pharmacy & bioallied sciencesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Recently, we have shown that small molecule dCK inhibitors in combination with pharmacological perturbations of de novo dNTP biosynthetic pathways could eliminate acute lymphoblastic leukemia cells in animal models. However, our previous lead compound had a short half-life in vivo. Therefore, we set out to develop dCK inhibitors with favorable pharmacokinetic properties. We delineated the sites of the inhibitor for modification, guided by crystal structures of dCK in complex with the lead compound and with derivatives. Crystal structure of the complex between dCK and the racemic mixture of our new lead compound indicated that the R-isomer is responsible for kinase inhibition. This was corroborated by kinetic analysis of the purified enantiomers, which showed that the R-isomer has >60-fold higher affinity than the S-isomer for dCK. This new lead compound has significantly improved metabolic stability, making it a prime candidate for dCK-inhibitor based therapies against hematological malignancies and, potentially, other cancers.
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What OpenQuestion holds
Registered trials
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.