DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for coronary stenosis — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCoronary stenosis maps to a 5-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
approvedAdenosineApproved drug
Structures already discussed alongside coronary stenosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of Phosphoribosylaminoimidazole carboxylase from Burkholderia xenovorans (AMP, ADP and sulfate complex) — Adenosine has a real, experimentally solved structure in complex with this target (PDB 10BM, 2.49 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet ampdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 10BM · 2.49 Å · ligand Adenosine (AMP). Experimental structure, not a prediction.
What the evidence adds up to
A 2015 study of 153 consecutive carotid endarterectomies found that severe coronary stenosis, defined by coronary computed tomography angiography, was an independent predictor of early adverse vascular outcome (stroke, myocardial infarction, or death within 30 days). Eight adverse events occurred: six strokes, two myocardial infarctions, and three deaths. The odds ratio for severe versus mild-to-moderate stenosis was 6.87 (95% confidence interval 1.20–39.22). Stratification by operative risk as defined in the SAPPHIRE trial did not yield a significant difference in outcome.
A 1997 rat model of non-occlusive coronary artery narrowing (average 55% reduction in luminal diameter) produced left ventricular failure and right ventricular dysfunction at 7 and 14 days. In isolated myocytes, beta-adrenoreceptor density decreased by 7 days, with a further reduction at 14 days affecting both beta-1 and beta-2 subtypes. The proportion of high-affinity binding sites fell at 14 days. Gs alpha function was not impaired, but Gi alpha quantity increased at both time points. Forskolin- and GTP-stimulated adenylyl cyclase activity was unchanged, yet basal cyclic AMP in myocytes was depressed at 14 days.
A 2014 review of 59 published studies on coronary computed tomography angiography found that 53 studies used a threshold of 50% or greater narrowing to define potentially significant stenosis, consistent with societal guidelines. However, only 18 of those 53 studies reported precisely according to the recommended thresholds of 50% or greater for moderate stenosis and 70% or greater for severe stenosis. The majority did not clearly describe the degree of stenosis, and six studies used alternative thresholds such as 20% to 75% or 40% to 70%.
A 2025 review argues that acute cardiovascular events frequently arise from stenoses exceeding 70%, but that the mortality inflection point for coronary heart disease has not been reached with revascularisation alone. It defines mild-to-moderate stenosis as less than 70% narrowing and notes that soft plaque and plaque rupture can cause events without haemodynamically significant stenosis. The review summarises detection methods, risk assessment, and proposed intervention strategies, but does not report new trial data or patient outcomes. What remains missing is prospective evidence that intervening on mild-to-moderate stenosis reduces mortality, as well as adequately powered trials that stratify patients by plaque characteristics rather than degree of luminal narrowing alone.
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 Neurology · 2015 · 11 citations · open access
Preoperative Coronary Stenosis Is a Determinant of Early Vascular Outcome after Carotid Endarterectomy
AbstractBACKGROUND AND PURPOSE: The benefit of carotid endarterectomy (CEA) is directly influenced by the risk of perioperative adverse outcomes. However, patient-level risks and predictors including coronary stenosis are rarely evaluated, especially in Asian patients. The aim of this study was to determine the relationship between the vascular risk factors underlying CEA, including coronary stenosis, and postoperative outcome. METHODS: One hundred and fifty-three consecutive CEAs from our hospital records were included in this analysis. All patients underwent coronary computed tomography angiography before CEA. Data were analyzed to determine the vascular outcomes in patients with mild-to-moderate vs. severe coronary stenosis and high vs. standard operative risk, based on the criteria for high operative risk defined in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial. The vascular outcome was defined as the occurrence of postoperative (≤30 days) stroke, myocardial infarction (MI), or death. RESULTS: An adverse vascular outcome occurred in 8 of the 153 CEAs, with 6 strokes, 2 MIs, and 3 deaths. The vascular outcome differed significantly between the groups with mild-to-moderate and severe coronary stenosis (p=0.024), but not between the high- and standard-operative-risk groups (stratified according to operative risk as defined in the SAPPHIRE trial). Multivariable analysis adjusting for potent predictors revealed that severe coronary stenosis (odds ratio, 6.87; 95% confidence interval, 1.20-39.22) was a significant predictor of the early vascular outcome. CONCLUSIONS: Severe coronary stenosis was identified herein as an independent predictor of an adverse early vascular outcome.
Coronary artery stenosis in rats affects β-adrenergic receptor signaling in myocytes
AbstractOBJECTIVE: The purpose of this study was to determine whether the early chronic ischemic cardiomyopathy produced by non-occlusive coronary artery constriction was characterized by alterations in the regulation of beta-adrenoreceptor (beta-AR) signaling. METHODS: Coronary artery narrowing was surgically induced in rats and the animals sacrificed at 7 and 14 days. The changes in the biochemical properties of the multiple components of the beta-AR pathway were examined in enzymatically dissociated myocytes. RESULTS: Coronary stenosis, involving an average 55% reduction in luminal diameter, was associated with left ventricular failure and right ventricular dysfunction at both time intervals. A decrease in the quantity of beta-AR was detected at 7 days and preceded the loss of high-affinity binding sites. This regulatory modification was characterized by a reduction in beta 1 and beta 2 receptors and a shift in the isoproterenol dose response curve indicating a functional correlation between the decrease in beta-AR and attenuated inotropic support of the myocardium. The percentage of beta-AR binding agonist with high affinity decreased significantly at 14 days along with a further reduction in the density of beta 1 and beta 2 receptors. Reconstitution studies with cyc S49 lymphoma cells did not detect an impairment of Gs alpha functional activity, but the quantity of Gi alpha was increased at both intervals. Finally, activation of the catalytic unit of adenylyl cyclase by forskolin and GTP was not altered by coronary stenosis, however, basal cyclic AMP in myocytes was depressed at 14 days. CONCLUSIONS: Coronary stenosis induces distinct and progressive modifications in the beta-AR signaling cascade which may contribute to the impaired ventricular performance in this model of myocardial ischemia.
A review of adherence to the guidelines for coronary CT angiography quantitative stenosis grading thresholds in published research
AbstractBACKGROUND: The degree of coronary stenosis of potential hemodynamic significance is central to the interpretation of coronary computed tomography angiography (CCTA), but has been variably defined in the literature. Societal guidelines have attempted to address this issue via recommended thresholds. OBJECTIVES: We surveyed the various thresholds for defining significant coronary stenosis reported in research published since the introduction of the Society for Cardiovascular Computed Tomography guidelines regarding the interpretation and reporting of CCTA. METHODS: We systematically reviewed the results of bibliographic searches of all original research articles on CCTA, focusing on studies reporting > 25 subjects, to assess the definitions of severity of coronary lesions as found on CCTA. To enable comparisons, we stratified the methods of reporting lesion severity into ≥ 50%, 50% to 69%, and "others" (including infrequent reporting methods). RESULTS: Fifty-nine11 published studies were identified and met inclusion criteria. Eighteen studies reported the severity of coronary stenosis using a definition of 50% to 69% as moderate stenosis; 35 studies defined ≥ 50% coronary stenosis as "stenosis," "significant stenosis," or "obstructive lesion" without distinguishing a threshold for moderate versus severe stenosis. Six studies utilized other thresholds, such as 20% to 75%, 40% to 69%, 40% to 70%, 40% to 79%, and 50% to 75% to define moderate coronary stenosis. CONCLUSIONS: Fifty-three of 59 studies were graded in accordance with the recommended threshold of ≥ 50% defining potentially significant stenosis, with 18 studies reporting precisely in accordance with the guidelines-recommended thresholds of ≥ 50% narrowing as defining moderate stenosis and ≥ 70% narrowing as defining severe stenosis. Six studies were reported using alternative thresholds for significant stenosis. However, a majority of research studies published since 2009 do not follow the societal guidelines for stenosis grading, since these studies do not clearly describe the degree of coronary stenosis.
Reviews in Cardiovascular Medicine · 2025 · 1 citations · open access
Current Advancements in the Diagnosis and Management of Mild-to-moderate Coronary Stenosis
AbstractCoronary heart disease (CHD) is associated with increased morbidity and mortality. Acute cardiovascular events frequently occur in patients with coronary artery stenoses exceeding 70%. Although coronary revascularization can significantly improve ischemic symptoms, the inflection point for reducing mortality from CHD has yet to be reached. Therefore, the prevention and treatment of mild-to-moderate coronary artery stenosis should be given significant attention to more effectively reduce the incidence and mortality of acute events from CHD. Subsequently, a stenosis of less than 70% is used to characterize the incidence of mild to moderate coronary artery stenosis. While acute cardiovascular events caused by soft plaque and plaque rupture may not have a significant impact on hemodynamics, these events are detrimental and result in increased mortality. This review summarizes the methods available for detecting mild-to-moderate coronary artery stenoses, assessing risk, and understanding the mechanisms underlying adverse events. Moreover, this review proposes intervention strategies for preventing and treating mild to moderate coronary stenosis.
Journal of Cardiovascular Magnetic Resonance · 2011 · 0 citations · open access
Evaluation of the significance of intermediate coronary artery stenoses by stress perfusion CMR
AbstractTo determine the feasibility of adenosine stress cardiac magnetic resonance (CMR) to guide clinical management of patients with a documented intermediate angiographic coronary stenosis. A number of patients undergoing assessment for possible ischaemic heart disease proceed straight to coronary angiography without prior non-invasive functional tests. When an intermediate coronary lesion is then encountered, the functional significance of that lesion is often unclear. Invasive assessment with fractional flow reserve can clarify the situation but is not always available and involves significant expense. Non-invasive tests are then frequently requested to guide treatment. Adenosine stress perfusion imaging has been shown to have a high sensitivity and specificity for detecting ischaemic heart disease. We sought to determine the ability of stress perfusion CMR to guide management in these patients. Retrospective analysis of patients with an intermediate coronary stenosis on angiogram subsequently referred for adenosine stress CMR. Patients with previous CABG were excluded. Only those with single vessel disease were evaluated. All intermediate lesions were in the range 30-70% on angiogram. Perfusion imaging was obtained at stress (adenosine 140 µg/kg/min) and rest on a 1.5T scanner. Late enhancement was assessed with dual pass gadolinium (0.2mmol/kg total dose). Patient records, hospital databases and national death registries were reviewed. We defined MACE as cardiovascular death, myocardial infarction, revascularisation, and ischaemic hospitalisation. Thirty nine patients, with follow up data for a median 25 months (IQR 22-28), were identified. Of those with a positive adenosine stress CMR, 69% (9 of 13) encountered MACE. These were all PCI events. Of those with a negative CMR, MACE occurred in 12% (3 of 26). These were also PCI events, however only two of these were symptom driven, due to lesion progression at 9 and 10 months respectively. Adenosine stress perfusion CMR may be a useful tool in the clinical management of patients with an intermediate coronary artery stenosis.
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.
