DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary antithrombin 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 moduleHereditary antithrombin 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 hereditary antithrombin 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
serpin family C member 1 (SERPINC1) — SERPINC1 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 z9ldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3KCG · 1.7 Å · ligand methyl 2,3,6-tri-O-sulfo-alpha-D-glucopyranoside (Z9L). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary antithrombin deficiency is a hypercoagulable state that increases the risk of venous thrombosis. The recommended initial diagnostic test is an activity (functional) assay. Acquired antithrombin deficiency is much more common than the hereditary form, so when activity is low, further steps are needed to confirm or exclude a hereditary cause. Direct thrombin inhibitors can produce falsely normal results. A 2010 review describes the advantages and disadvantages of the various testing options and the appropriate confirmatory steps.
Twenty-two novel mutations in the SERPINC1 gene were reported in 2006 from 17 French and five German families with antithrombin deficiency, all present in the heterozygous state. Nine missense mutations caused type I deficiency, defined by equally low activity and antigen levels. Seven of these nine affected highly conserved serpin residues and were associated with venous thrombosis occurring before age 32. Other type I causes included one splice site mutation, one nonsense mutation, three small deletions, and one insertion. Seven other missense mutations were identified in type II or unclassified deficiency, affecting the heparin binding region, the pleiotropic region, the signal peptide, a disulfide bond, or a nonconserved residue on strand 2C.
A 1999 review placed antithrombin deficiency in the context of the complex genetic basis for venous thrombosis, highlighting work on mutations within the antithrombin signal peptide. The review did not provide new clinical trial data.
No treatment trials are reported in these abstracts. No data on survival, response rates, or sample sizes for any intervention are given. What is missing is any randomised trial testing a drug or management strategy in hereditary antithrombin deficiency, as well as patient stratification by mutation type or thrombosis history.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Hematology · 2010 · 130 citations · open access
Molecular bases of antithrombin deficiency: twenty-two novel mutations in the antithrombin gene
AbstractAntithrombin (AT) is a major physiological inhibitor of hemostasis. We report 22 novel antithrombin gene (SERPINC1) mutations associated with antithrombin deficiency in 17 French and five German families. They were all present at the heterozygous state. Nine missense mutations accounted for type I deficiency, defined by equally low antithrombin activity and antigen level. Most of them (7/9) affected highly conserved serpin residues and were associated with venous thrombosis occurring at a young age (before age 32). One splice site, one nonsense mutation, three small deletions and one insertion were also identified as a cause for type I antithrombin deficiency. Seven other missense mutations were identified in type II or unclassified AT deficiency; g.5270C>T (p.T147I, T115I) and g.5281A>T (p.I151F, I119F) change residues in the heparin binding region, g.13267C>G (p.P439A, P407A) and g.13271T>C (p.F440S, F408S) affect amino acids in the pleiotropic region, g.2372G>A (p.G25D, G-8D) changes a signal peptide amino acid, g.2456G>C (p.C53S, C21S) affects one of the three disulfide bonds of the protein, and g.7585A>T (p.M347K, M315K) changes a nonconserved residue on strand 2C.
European Journal Of Haematology · 2005 · 7 citations · open access
Successful therapy with argatroban for superior mesenteric vein thrombosis in a patient with congenital antithrombin deficiency
AbstractA 38-year-old woman was admitted with superior mesenteric vein (SMV) thrombosis, which was refractory to anticoagulation therapy. The plasma antithrombin activity was decreased and hardly compensated by concentrated antithrombin preparation due to high consumption rate. However, successful anticoagulation was achieved by administration of direct thrombin inhibitor, argatroban. Family studies of antithrombin activity revealed that she had type I congenital antithrombin deficiency. A novel heterozygous mutation in the gene for antithrombin (single nucleotide T insertion at 7916 and 7917, Glu 272 to stop in exon 4) was identified. Argatroban administration would be effective in the treatment of congenital antithrombin deficiency with SMV thrombosis.
Japanese Journal of Thrombosis and Hemostasis · 1999 · 0 citations · open access
Antithrombin and the Complex Genetic Basis of Venous Thrombosis.
AbstractIn this review, we consider the contribution of antithrombin deficiency to venous thrombosis, highlighting some recent work from our laboratory on mutations within the antithrombin signal peptide. In addition, we place antithrombin deficiency in the context of a contributor to the complex genetic basis for the phenotype of venous thrombosis. Recent reviews provide coverage of other aspects of antithrombin and venous thrombosis.
AbstractThe clinical importance of antithrombin was directly proved by the description of the first hereditary antithrombin deficiency /HAD/ in 1965. Several other families have been studied since that time. Two main types of /HAD/ can be discerned. In one, both immunologic and fuctional methods reveal low level of antithrombin in the affected members. Some biochemical observations suggest the heterogenity even of this type of HAD. Oral anticoagulants seem effective in the treatment and prophylaxis of these patients. Thus, determination of antithrombin level should be performed in all young thrombotic patients especially. with prevalence of thromboembolism in the family. The second type of HAD, the congenital functional abnormality of antithrombin is very rare. Oestrogenic hormones can decrease the synthesis of antithrombin. This observation might be connected with •the thromboembolic complications of oral contraceptives. More data ar needed to evaluate the usefulness of monitoring the antithrombin level in the course of contraceptive treatment to avoid these complications. Decreased antithrombin levels and detection of antithrombin-complexes can provide useful information in the diagnosis of hypercoagulable states. Due to the methodologic development experienced in the last few years, one can expect a rapid rise of clinical investigations bringing about a better knowledge of clinical significance.
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.
