DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyper-IgM syndrome type 5 — 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 moduleHyper-IgM syndrome type 5 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 hyper-igm syndrome type 5 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
uracil DNA glycosylase (UNG) — UNG 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 uradrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1EMJ · 2.0 Å · ligand URACIL (URA). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Allergy and Clinical Immunology · 2002 · 38 citations
Cross-talk between CD40 and CD40L: lessons from primary immune deficiencies
AbstractPURPOSE OF REVIEW: The purpose of this review is to provide an update of the molecular bases of CD40-mediated signalling and of the human immune defects associated with abnormalities of this activation pathway. RECENT FINDINGS: Over the last years considerable progress in the identification of intracellular molecules mediating CD40 signalling has been achieved. This review focuses on the recent work on the molecular mechanisms of CD40 signalling mediated by tumor necrosis factor receptor-associated factors, by transcription of the activation-induced cytidine deaminase gene and by activation of nuclear factor kappa B. Furthermore, the importance of CD40/CD40L interaction for the induction of adaptive immunity will be outlined in the context of primary immunodeficiencies due to defects of the genes involved in the CD40 signalling pathway, which are characterized by an immunological phenotype of hyper-IgM syndrome. SUMMARY: The critical role of CD40/CD40L interactions in the development of various disease states has been fully appreciated, and further understanding of the molecular events involved in CD40 signalling may allow the identifications of candidate genes for other hyper-IgM syndromes. Molecular diagnosis will help to provide the most appropriate treatment and prognosis.
Three novel mutations reflect the variety of defects causing phenotypically diverse X-linked hyper-IgM syndrome
AbstractX-linked hyper-IgM syndrome (HIGM1) (MIM musical sharp 308230), is a severe primary immunodeficiency caused by mutations in the gene coding for CD40 ligand (CD40L or CD154), a member of the tumour necrosis factor (TNF) superfamily. The interaction of this protein with its ligand, CD40, mediates crucial processes in the immune response. The variety of defects that have been described in HIGM1 patients range from a complete lack of CD40L protein expression to missense mutations that interfere with its interaction with CD40L. In this study we describe three families - a total of seven HIGM1 patients and carriers, presenting a spectrum of severity in clinical evolution. In two of these families, patient DNA samples were available for genetic studies. In the third, carrier detection was performed on female family members. The results of immunological studies - the different patterns of CD40L expression and binding capacity as measured by flow cytometry - and molecular diagnosis are presented. Three novel mutations were identified: an intron mutation that partially interferes with the splicing process (intron 3, position + 5 G/T); a missense mutation (Ser222 Phe) located in the molecular region which interacts with the receptor and which abrogates binding capacity; and a 14 base pair deletion leading to a frameshift and a premature truncated mutation (del I 171 X 195). An attempt to correlate protein expression and function of the CD40L mutants with clinical disease evolution is described.
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.
