DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for adenosine kinase deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAdenosine kinase deficiency maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for adenosine kinase deficiency is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
adenosine kinase (ADK) — ADK is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet beta-d-ribofuranosyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4O1L · 2.5 Å · ligand 5-ethynyl-7-(beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (HO4). Experimental structure, not a prediction.
What the evidence adds up to
The 1996 cloning papers established the primary structure of human adenosine kinase, a 345-amino-acid, 38.7 kDa enzyme that phosphorylates adenosine to AMP. The cDNA was obtained from lymphocyte, placental, and liver libraries, and two mRNA species (1.3 and 1.8 kb) were found in all tissues examined, attributable to alternative polyadenylylation sites. Sequence comparisons showed no similarity to other mammalian nucleoside kinases, but two regions shared significant identity with microbial ribokinase, fructokinase, and a bacterial inosine/guanosine kinase, suggesting adenosine kinase is structurally akin to microbial sugar kinases. In Chinese hamster ovary cells, transfection of the cloned cDNA into an adenosine-kinase-deficient mutant restored enzyme activity and reversed resistance to the adenosine analog toyocamycin, making the transformed cells as sensitive to the analog as wild-type cells. One class of mutant lacking adenosine kinase activity arose at a spontaneous frequency of 10⁻⁴ to 10⁻³ and involved gross structural alterations in the gene; another class, resistant only to C-adenosine analogs, did not show such alterations.
A 1993 paper (misdated in the abstract list; the content describes a screening study) reported development of a new adenosine kinase assay and screening of a focused compound library, yielding 12 hit compounds (a 6% hit rate) representing six new classes of non-nucleoside human adenosine kinase inhibitors. The most potent inhibitor had a Ki of 184 nM. The authors concluded that the new assay was useful for discovering novel inhibitors that might serve as lead structures for adenosine augmentation therapy. No clinical data, patient outcomes, or in vivo results were presented in any of these abstracts.
What is still missing: any clinical trial in adenosine kinase deficiency, any patient-derived data, any in vivo efficacy or toxicity testing of the identified inhibitors, and any evidence that the non-nucleoside inhibitors reach relevant tissues or alter disease course. Funding for translational work and a defined patient stratification strategy are absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Biological Chemistry · 1967 · 157 citations · open access
Some Properties of Partially Purified Mammalian Adenosine Kinase
AbstractAbstract Adenosine kinase has been partially purified from homogenates of rabbit liver and Ehrlich ascites tumor cells. The kinase preparation obtained was free of adenosine deaminase and almost free of adenosine triphosphatase activity. In addition to adenosine, 34 analogues or derivatives of adenosine have been investigated with the enzyme. Of these compounds, 16 were substrates, and the Michaelis constants and maximal velocities of these substrates have been determined. In the presence of myokinase, at least 10 compounds were further phosphorylated to the corresponding triphosphates.
Proceedings of the National Academy of Sciences · 1996 · 127 citations · open access
Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases.
AbstractAdenosine kinase catalyzes the phosphorylation of adenosine to AMP and hence is a potentially important regulator of extracellular adenosine concentrations. Despite extensive characterization of the kinetic properties of the enzyme, its primary structure has never been elucidated. Full-length cDNA clones encoding catalytically active adenosine kinase were obtained from lymphocyte, placental, and liver cDNA libraries. Corresponding mRNA species of 1.3 and 1.8 kb were noted on Northern blots of all tissues examined and were attributable to alternative polyadenylylation sites at the 3' end of the gene. The encoding protein consists of 345 amino acids with a calculated molecular size of 38.7 kDa and does not contain any sequence similarities to other well-characterized mammalian nucleoside kinases, setting it apart from this family of structurally and functionally related proteins. In contrast, two regions were identified with significant sequence identity to microbial ribokinase and fructokinases and a bacterial inosine/guanosine kinase. Thus, adenosine kinase is a structurally distinct mammalian nucleoside kinase that appears to be akin to sugar kinases of microbial origin.
European Journal of Biochemistry · 1996 · 34 citations
Cloning and Characterization of cDNA for Adenosine Kinase from Mammalian (Chinese Hamster, Mouse, Human and Rat) Species.
AbstractThe enzyme adenosine kinase constitutes the major purine nucleoside phosphorylating activity in mammalian cells. In view of its central role in adenosine metabolism, which is an important physiological regulator, an understanding of the primary structure of adenosine kinase is of much interest. Using microsequence information from peptides derived from purified Syrian hamster liver enzyme, we have succeeded in isolating full length cDNA clones encoding adenosine kinase from Chinese hamster ovary cells and mouse 3T3 cells. The open reading frames in these clones consist of 334 and 335 amino acids and encode proteins of molecular masses 37364 Da and 37489 Da, respectively. In addition, the coding and upstream sequences for adenosine kinase from human (HeLa cells) and rat liver have also been cloned and sequenced. Transfection of an adenosine-kinase-deficient mutant (selected for resistance to the adenosine analog toyocamycin) of Chinese hamster ovary cells with a plasmid containing the cloned adenosine kinase cDNA, leads to regaining of adenosine kinase activity in the transformed cell. The adenosine kinase transformants also simultaneously lost their toyocamycin resistance and became similarly sensitive to the analog as the parental wild-type Chinese hamster ovary cells. The cloned adenosine kinase cDNA was also used to examine structural changes in mutants affected in adenosine kinase. In Chinese hamster ovary cells, one type of mutant that lacks adenosine kinase activity and displays high degree of resistance to various adenosine analogs, is obtained at an unusually high spontaneous frequency (10(-4)-10(-3)). Results of Southern and northern-blot analysis provide evidence that this group of mutants involves gross structural alterations affecting the adenosine kinase gene. Such structural alterations are not observed in another type of mutant which exhibits increased resistance only to C-adenosine analogs. Sequence similarity searches indicate that several of the bacterial and yeast sugar kinases (ribokinase, fructokinase and inosine-guanosine kinase) exhibit limited but significant similarity to the mammalian adenosine kinase. The sequence similarity data support the possibility that adenosine kinase shares a common evolutionary ancestor with these protein sequences.
European Journal of Biochemistry · 1996 · 28 citations
Cloning and Characterization of cDNA for Adenosine Kinase from Mammalian (Chinese Hamster, Mouse, Human and Rat) Species
AbstractThe enzyme adenosine kinase constitutes the major purine nucleoside phosphorylating activity in mammalian cells. In view of its central role in adenosine metabolism, which is an important physiological regulator, an understanding of the primary structure of adenosine kinase is of much interest. Using micro‐sequence information from peptides derived from purified Syrian hamster liver enzyme, we have succeeded in isolating full length cDNA clones encoding adenosine kinase from Chinese hamster ovary cells and mouse 3T3 cells. The open reading frames in these clones consist of 334 and 335 amino acids and encode proteins of molecular masses 37364 Da and 37489 Da, respectively. In addition, the coding and upstream sequences for adenosine kinase from human (HeLa cells) and rat liver have also been cloned and sequenced. Transfection of an adenosine‐kinase‐deficient mutant (selected for resistance to the adenosine analog toyocamycinj of Chinese hamster ovary cells with a plasmid containing the cloned adenosine kinase cDNA, leads to regaining of adenosine kinase activity in the transformed cell. The adenosine kinase transformants also simultaneously lost their toyocamycin resistance and became similarly sensitive to the analog as the parental wild‐type Chinese hamster ovary cells. The cloned adenosine kinase cDNA was also used to examine structural changes in mutants affected in adenosine kinase. In Chinese hamster ovary cells, one type of mutant that lacks adenosine kinase activity and displays high degree of resistance to various adenosine analogs, is obtained at an unusually high spontaneous frequency 10 −4 ‐ 10 −3 ). Results of Southern and northern‐blot analysis provide evidence that this group of mutants involves gross structural alterations affecting the adenosine kinase gene. Such structural alterations are not observed in another type of mutant which exhibits increased resistance only to C‐adenosine analogs. Sequence similarity searches indicate that several of the bacterial and yeast sugar kinases (ribokinase, fructokinase and inosine‐guanosine kinase) exhibit limited but significant similarity to the mammalian adenosine kinase. The sequence similarity data support the possibility that adenosine kinase shares a common evolutionary ancestor with these protein sequences.
A Study of Mathematics Education in the Lutheran Church-Missouri Synod Schools Using Background Questions from the 1990 National Assessment of Educational Progress.
AbstractAdenosine kinase (AdK) is a key player in controlling intra- and extracellular concentrations of the signaling molecule adenosine. Extensive evidence points to an important role of AdK in several diseases, and suggests that AdK inhibition might be a promising therapeutic strategy. The development of a new AdK assay and subsequent screening of part of our focused compound library led to the identification of 12 hit compounds (hit rate of 6%) representing six new classes of non-nucleoside human AdK inhibitors. The most potent inhibitor 1 displayed a K<sub>i</sub> value of 184nM. Compound screening with a newly developed assay was useful and efficient for discovering novel AdK inhibitors which may serve as lead structures for developing drugs for adenosine augmentation therapy.
Zenodo (CERN European Organization for Nuclear Research) · 2021 · 0 citations · open access
METADATA: Marie Skłodowska-Curie Action, DADA2GT, Project Number: 841780
AbstractThis repository contains the data generated through the Marie Skłodowska-Curie Action DADA2GT (Project Number: 841780) entitled "Development of gene therapy and genome editing strategies to treat adenosine deaminase 2 deficiency." All the data are stored as .cvs files. The results of the Action have been included in the publication entitled "Lentiviral correction of enzymatic activity restrains macrophage inflammation in adenosine deaminase 2 deficiency" published in the open-access journal Blood Advances and available at https://doi.org/10.1182/bloodadvances.2020003811 and Zenodo.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
