DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital factor XI 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 moduleCongenital factor XI 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 congenital factor xi 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
coagulation factor XI (F11) — F11 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I58 · 2.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1982 case report describes a patient with congenital factor XI deficiency who developed a high-titre acquired inhibitor (6,000 U/ml) after plasma infusion, presenting with a spontaneous thigh bleed that progressed despite fresh frozen plasma. The bleed responded promptly to activated prothrombin complex. The inhibitor was isolated as polyclonal IgG, predominantly subclass 4, with an affinity constant of 1.65 x 10^10 L/mol for factor XI, and was shown to block factor XI binding to high molecular weight kininogen, its activation by factor XIIa, and its subsequent activation of factor IX. Notably, the patient had only two documented haemorrhages despite the inhibitor, a milder clinical course than typical severe factor VIII or IX deficiency, leading the authors to propose independent bypass mechanisms for factors XII and XI in normal haemostasis.
A 1993 report documents an uncomplicated pregnancy and successful childbirth in a woman with congenital factor XI deficiency and an acquired inhibitor, noting the persistence of residual factor XI activity despite the inhibitor's presence. This suggests that some circulating factor XI function can remain even with an inhibitor, which may explain the relatively mild bleeding phenotype in some patients. The report does not provide quantitative factor XI levels or inhibitor titres during pregnancy.
A 2012 family study identified a novel F11 missense mutation, Ile463Ser, in exon 12, found in heterozygosity in an asymptomatic 19-year-old proband diagnosed during presurgical screening and in his asymptomatic mother. The mutation lies in the serine protease catalytic domain and was deemed responsible for the low factor XI levels in both individuals. No bleeding symptoms were reported in either carrier.
Across these reports, the key missing elements are prospective data on bleeding risk in inhibitor patients, standardised management protocols for pregnancy and surgery, and genotype-phenotype correlation for mutations like Ile463Ser. No trial has systematically tested bypassing agents or factor XI replacement in inhibitor patients, and the rarity of the condition means no randomised evidence exists. What is still needed is a registry of inhibitor patients with longitudinal outcomes, functional assays that distinguish residual factor XI activity from inhibitor neutralisation, and a consensus on when activated prothrombin complex concentrate is indicated versus watchful waiting.
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 Clinical Investigation · 1982 · 44 citations · open access
Acquired Antibody to Factor XI in a Patient with Congenital Factor XI Deficiency
AbstractThe results of studies in a patient with congenital deficiency of Factor XI who developed an inhibitor are presented. The patient presented with a severe, apparently spontaneous bleed into the thigh, which progressed despite infusion of fresh frozen plasma, but which responded promptly to activated prothrombin complex. During therapy with plasma his clotting time and Factor XI level were unresponsive and a Factor XI inhibitor titer of 6,000 U/ml was attained. The inhibitor was isolated and found to be polyclonal immunoglobulin G (IgG), predominantly of subclass 4. The specificity of the antibodies for Factor XI was shown by the ability of isolated inhibitor bound to polyacrylamide beads to remove Factor XI selectively from normal plasma. The binding of (125)I-labeled factor XI to the inhibitor was studied and an affinity constant of 1.65 x 10(10) liter/mol was found. Complexing of the antibodies with Factor XI was shown to block multiple activities of the clotting factor. Factor XI complexed with antibody did not bind to high molecular weight kininogen or undergo activation and cleavage by two-chain Factor XII. The complex of activated Factor XI with inhibitor prevented the cleavage and activation of Factor IX. Hence the inhibitor appears to act by binding to multiple sites on the Factor XI molecule and preventing its interaction with other molecules. Clinically these interactions of the inhibitor with Factor XI result in a state of severe Factor XI deficiency. The clinical circumstances of the case, with severe hemorrhage refractory to plasma infusion but readily responsive to an alternate clot-promoting agent, suggest that a defect of intrinsic system activation was critical, supporting the inference that Factor XI does participate in normal hemostasis. The clinical course of this patient, who has only had two documented hemorrhages in the presence of the inhibitor, is not as severe as that of patients with severe Factor VIII or IX deficiency. This suggests that physiologic activation of Factors XI and IX does not occur exclusively in series because deficiency of factors XII, XI, VIII, and IX should then have similar hemostatic consequences. We propose that independent mechanisms for bypass of Factors XII and XI are important in physiologic activation of coagulation.
AbstractCongenital sensory neuropathy with anhidrosis (CSNA) is a well-defined entity among a group of sensory deficiency syndromes. Children with this genetic disease are insensitive to pain and temperature, do not sweat, and suffer from mental retardation. Self-mutilation may be severe and may lead to insoluble orthopedic problems. We treated a girl with CSNA, who was born to nonconsanguineous Japanese parents. This disease is important in the dermatological field, since the degree of anhidrosis and self-mutilation influence the prognosis of patients with CSNA.
British Journal of Haematology · 1993 · 16 citations
Successful childbirth by a patient with congenital factor XI deficiency and an acquired inhibitor
AbstractAcquired inhibitors in factor XI deficiency (FXI) are rare. The presence of an inhibitor during pregnancy poses a potential haemorrhagic risk to the fetus. We report an uncomplicated pregnancy and successful childbirth by a woman with congenital FXI deficiency and an acquired inhibitor, and discuss the persistence of residual FXI activity in the presence of an inhibitor.
Identification of a novel F11 missense mutation (Ile463Ser) in a family with congenital factor XI deficiency
AbstractWe investigated an asymptomatic 19-year-old patient with factor XI deficiency diagnosed in the context of presurgical laboratory screening. The F11 gene was analyzed and a novel missense mutation I463S in exon 12 was identified in heterozygosity in the proband. His mother, also diagnosed with asymptomatic factor XI deficiency, was found to be heterozygous for the same mutation. This novel amino acid substitution in the serine protease catalytic domain appears to be responsible for the low factor XI levels in both individuals.
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.
