DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for emphysema — screening already-approved drugs against its 33-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEmphysema maps to a 33-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 emphysema 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
transforming growth factor beta receptor 2 (TGFBR2) — TGFBR2 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 6-methoxypyridin-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5QIN · 1.57 Å · ligand N-{4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide (J2V). Experimental structure, not a prediction.
What the evidence adds up to
In 2008 a study of lung tissue from non-smokers, smokers without emphysema, and smokers with emphysema found that Nrf2 protein levels were significantly decreased in whole lung and in alveolar macrophages of patients with emphysema, while Bach1 and Keap1 levels were increased. These changes were accompanied by reduced expression of the antioxidant proteins HO-1, GPX2 and NQO1, and the degree of reduction correlated with airway obstruction and lung distension. Silencing RNA experiments in THP-1 cells confirmed that loss of Nrf2 directly caused the decrease in those antioxidant enzymes. The authors concluded that the Nrf2/Keap1-Bach1 equilibrium is altered in emphysema, pointing to a diminished stress response phenotype and suggesting that restoring that equilibrium might be a therapeutic target.
A 2025 review of emphysema covers risk factors, mechanisms, experimental models and available therapeutics, and mentions exploratory approaches aimed at evidence-based and personalised medicine. It does not report any new clinical trial results or specific drug outcomes.
A 2011 trial of Exhale airway bypass stents for severe homogeneous emphysema was a multicentre, double-blind, randomised, sham-controlled study at 38 centres worldwide that enrolled 315 patients. The abstract does not report efficacy or safety results, only the trial design.
What is still missing is any clinical trial that tests a drug designed to restore the Nrf2/Keap1-Bach1 equilibrium in patients with emphysema, and no such agent has been shown to improve lung function or survival in a randomised controlled setting. The 2011 stent trial results are not given, so its efficacy remains unknown from this abstract. No drug therapy has been proven to reverse alveolar destruction or alter the natural history of emphysema.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Thorax · 2008 · 193 citations · open access
Altered Nrf2/Keap1-Bach1 equilibrium in pulmonary emphysema
AbstractBACKGROUND: Oxidative stress, resulting from the increased oxidative burden and decreased level of antioxidant proteins, plays a role in the pathophysiology of smoking-related pulmonary emphysema. Expression of several antioxidant proteins, such as heme oxygenase-1 (HO-1), glutathione peroxidase 2 (GPX2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), results from an equilibrium created by positive or negative regulation by the transcription factors Nrf2, Keap1 and Bach1, respectively. However, whether the expression of these transcription factors is altered in emphysema and could account for decreased expression of antioxidant proteins is not known. A study was undertaken to investigate the expression and subcellular localisation of Nrf2, Keap1 and Bach1 as potential regulators of HO-1, GPX2 and NQO1 in alveolar macrophages, a key cell in oxidative stress, in lung surgical specimens from non-smokers without emphysema and smokers with and without emphysema. METHODS AND RESULTS: Western blot, immunohistochemical and laser scanning confocal analysis revealed that the Nrf2 protein level decreased significantly in whole lung tissue and alveolar macrophages (cytosol and nucleus) in patients with emphysema compared with those without emphysema. Conversely, Bach1 and Keap1 levels were increased in patients with emphysema. These modifications were associated with a parallel decrease in the expression of HO-1, GPX2 and NQO1 at the cellular level, which was inversely correlated with airway obstruction and distension indexes, and increased macrophage expression of the lipid peroxidation product 4-hydroxy-2-nonenal. Silencing RNA experiments in vitro in THP-1 cells were performed to confirm the cause-effect relation between the loss of Nrf2 and the decrease in HO-1, NQO1 and GPX2 expression. Nrf2/Keap1-Bach1 equilibrium was altered in alveolar macrophages in pulmonary emphysema, which points to a decreased stress response phenotype. CONCLUSIONS: This finding opens a new view of the pathophysiology of emphysema and could provide the basis for new therapeutic approaches based on preservation and/or restoration of such equilibrium.
Pulmonary Emphysema: Current Understanding of Disease Pathogenesis and Therapeutic Approaches
AbstractPulmonary emphysema, the main component of chronic obstructive pulmonary disease, is a chronic lung inflammatory disease characterized by the loss of lung elasticity and impaired gas exchange due in large part to the destruction of alveolar walls. Cigarette smoking represents the most frequent etiologic factor, but other factors involving environmental pollution and respiratory infections contribute to disease pathogenesis and worsening. In this review, we provide a review about emphysema covering risk factors; underlying mechanisms of disease pathogenesis; experimental models that mimic, as closely as possible, human disease features; and available therapeutics. Lastly, exploratory therapeutic approaches aimed at improving patient health through evidence-based and personalized medicine are presented as well.
AbstractExisting treatment options for severe homogenous emphysema are limited, with dynamic airways collapse and gas trapping minimising the benefits of drug therapy. There has been interest in therapies that address these features more directly. The bronchoscopic lung volume reduction with Exhale airway stents for emphysema trial study group recently reported their findings in The Lancet . The group undertook a multicentre, double-blind, randomised, sham-controlled trial at 38 specialist respiratory centres worldwide. Three hundred and fifteen …
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.
