DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for UV-sensitive syndrome — 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 moduleUV-sensitive syndrome 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 uv-sensitive syndrome 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
ERCC excision repair 8, CSA ubiquitin ligase complex subunit (ERCC8) — ERCC8 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8B3D · 2.6 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). 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.
Proceedings of the National Academy of Sciences · 2004 · 181 citations · open access
Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome
AbstractUV-sensitive syndrome (UVsS) is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. UVsS cells show UV hypersensitivity and defective transcription-coupled DNA repair of UV damage. It was suggested that UVsS does not belong to any complementation groups of known photosensitive disorders such as xeroderma pigmentosum and Cockayne syndrome (CS). To identify the gene responsible for UVsS, we performed a microcell-mediated chromosome transfer based on the functional complementation of UV hypersensitivity. We found that one of the UVsS cell lines, UVs1KO, acquired UV resistance when human chromosome 10 was transferred. Because the gene responsible for CS group B (CSB), which involves neurological abnormalities and photosensitivity as well as a defect in transcription-coupled DNA repair of UV damage, is located on chromosome 10, we sequenced the CSB gene from UVs1KO and detected a homozygous null mutation. Our results indicate that previous complementation analysis of UVs1KO was erroneous. This finding was surprising because a null mutation of the CSB gene would be expected to result in CS features such as severe developmental and neurological abnormalities. On the other hand, no mutation in the CSB cDNA and a normal amount of CSB protein was detected in Kps3, a UVsS cell line obtained from an unrelated patient, indicating genetic heterogeneity in UVsS. Possible explanations for the discrepancy in the genotype-phenotype relationship in UVs1KO are presented.
Proceedings of the National Academy of Sciences · 2009 · 137 citations · open access
A UV-sensitive syndrome patient with a specific <i>CSA</i> mutation reveals separable roles for CSA in response to UV and oxidative DNA damage
AbstractUV-sensitive syndrome (UV(S)S) is a recently-identified autosomal recessive disorder characterized by mild cutaneous symptoms and defective transcription-coupled repair (TC-NER), the subpathway of nucleotide excision repair (NER) that rapidly removes damage that can block progression of the transcription machinery in actively-transcribed regions of DNA. Cockayne syndrome (CS) is another genetic disorder with sun sensitivity and defective TC-NER, caused by mutations in the CSA or CSB genes. The clinical hallmarks of CS include neurological/developmental abnormalities and premature aging. UV(S)S is genetically heterogeneous, in that it appears in individuals with mutations in CSB or in a still-unidentified gene. We report the identification of a UV(S)S patient (UV(S)S1VI) with a novel mutation in the CSA gene (p.trp361cys) that confers hypersensitivity to UV light, but not to inducers of oxidative damage that are notably cytotoxic in cells from CS patients. The defect in UV(S)S1VI cells is corrected by expression of the WT CSA gene. Expression of the p.trp361cys-mutated CSA cDNA increases the resistance of cells from a CS-A patient to oxidative stress, but does not correct their UV hypersensitivity. These findings imply that some mutations in the CSA gene may interfere with the TC-NER-dependent removal of UV-induced damage without affecting its role in the oxidative stress response. The differential sensitivity toward oxidative stress might explain the difference between the range and severity of symptoms in CS and the mild manifestations in UV(s)S patients that are limited to skin photosensitivity without precocious aging or neurodegeneration.
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.
