DeCure for Multiple cutaneous and mucosal venous malformations
DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for multiple cutaneous and mucosal venous malformations — 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 moduleMultiple cutaneous and mucosal venous malformations 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 multiple cutaneous and mucosal venous malformations 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
TEK receptor tyrosine kinase (TEK) — TEK 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 ndgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2GY5 · 2.9 Å · ligand 2-acetamido-2-deoxy-alpha-D-glucopyranose (NDG). Experimental structure, not a prediction.
What the evidence adds up to
In two large families with inherited venous malformations, a specific R849W missense mutation was found in the first kinase domain of the endothelial receptor tyrosine kinase Tie2, and the same mutation co-segregated with disease in one of four newly identified kindreds. A second family carried a different Tie2 mutation, Y897S, and both mutations caused ligand-independent hyperphosphorylation in COS-1 cell transfections, suggesting a gain-of-function mechanism. Two other families with the same inherited condition lacked any Tie2 mutation, and one of them excluded linkage to the TIE2 locus altogether, establishing at least one additional causal gene for dominantly inherited venous malformations.
Most venous malformations are sporadic (94%), and about 40% of sporadic cases are caused by a somatic mutation of the TEK gene. In a series of six patients who each presented with a single cutaneous venous malformation, gastrointestinal tract involvement appeared 3 to 10 years after the skin diagnosis. The authors argue that even a single skin lesion warrants early investigation for visceral disease, because gastrointestinal bleeding, anaemia, and consumptive coagulopathy can require emergency treatment.
For treatment of venous malformations at the hand, two case reports describe percutaneous sclerotherapy with sodium tetradecyl sulfate as one option among antithrombotic medication, local compression, and surgical resection. The report notes that therapy for venous malformations differs fundamentally from that for vascular tumours such as haemangiomas.
What remains missing is a prospective trial that tests whether early screening for gastrointestinal involvement in patients with a single cutaneous venous malformation reduces bleeding or emergency admissions. No randomised comparison of sclerotherapy agents or of sclerotherapy versus surgery exists for this specific inherited condition. The genetic heterogeneity — at least two loci, with gain-of-function Tie2 mutations in some families and an unknown gene in others — means that any future drug targeting the Tie2 pathway would need to account for patients who lack that mutation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Molecular Genetics · 1999 · 131 citations
Allelic and locus heterogeneity in inherited venous malformations
AbstractVenous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In two large unrelated kindreds mapping to chromosome 9, the identical R849W missense mutation was identified in the first kinase domain of Tie2, an endothelial cell-specific receptor tyrosine kinase. We report here the identification of four new kindreds with inherited venous malformations. Unlike the initial two families described, these four families demonstrate allelic and locus heterogeneity. In one of these families, the R849W mutation co-segregates with the disease phenotype. Three other families with venous malformations lack this mutation. One of these families is linked to markers near TIE2 on chromosome 9. In this family, we identified a novel mutation within the first kinase domain of Tie2 resulting in a Y897S change. Results from COS-1 cell transfections using expression constructs containing either the R849W or the Y897S mutation suggest that the receptors containing either mutation show ligand-independent hyperphosphorylation. These results suggest a gain-of-function mechanism for development of venous malformations in these families. Of the two remaining families, one excludes linkage to the TIE2 locus, establishing the existence of at least one additional locus for dominantly inherited venous malformations.
Die intraläsionale Sklerosierung venöser Malformationen an der Hand mit Natriumtetradecylsulfat
AbstractCongenital venous malformations (VM) at the hand are rare. VM consist of dysplastic venous vessels without progressive cellular proliferation. The therapy for VM is considerably different from that for vascular tumours (e. g., haemangiomas). Treatment options for vascular malformations are antithrombotic medication, local compression, resection of the VM, and obliteration of the lumina by percutaneous sclerosation. Here, the percutaneous sclerosation for the treatment of VM with sodium tetradecyl sulfate has been illustrated and discussed on the basis of 2 case reports.
Cutaneous venous malformations as a clue for possible gastrointestinal tract involvement: Diagnosis and treatment of six cases
AbstractVenous malformation (VM) is the most common type among vascular malformations classified by the International Society for the Study of Vascular Anomalies. Most VMs are sporadic (94%), caused in 40% of cases by somatic mutation of TEK gene. VMs can be cutaneous, visceral, or combined. Visceral involvement is rare, and gastrointestinal (GI) tract is the most common localization. Visceral VMs, usually asymptomatic, may manifest with bleeding, anemia, and consumptive coagulopathy, which sometimes require an emergency treatment. Our aim is to study the possible GI involvement in patients with only one cutaneous VM. We analyzed a series of six patients who presented with a single cutaneous VM and have subsequently manifested intestinal involvement at our reference center for vascular anomalies since 2010. In our patients, cutaneous VMs were located on lower or upper limbs, and GI involvement manifested from 3 to 10 years after skin diagnosis. Our experience urges to early diagnose a GI involvement also in patients with only one skin VM and to prevent severe complications. A multidisciplinary approach is mandatory for the diagnosis and treatment of these patients.
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.
