DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for coronary artery disease — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCoronary artery disease maps to a 43-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
Structures already discussed alongside coronary artery disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
NCS-1 — Dipyridamole has a real, experimentally solved structure in complex with this target (PDB 9T0H, 1.91 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 h9fdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9T0H · 1.91 Å · ligand Dipyridamole (H9F). Experimental structure, not a prediction.
What the evidence adds up to
A 2003 microarray study of nine severely atherosclerotic and six non-atherosclerotic human coronary arteries found 56 genes with differential expression in atherosclerotic tissue. Fifty-five of those genes were upregulated; only one, GST, was downregulated. Forty-nine of the associations were described as novel, including genes for ICAM-2, PIM-2, ECGF1, cathepsins K and H, and flavocytochrome 558. No survival or response data were reported because the study was purely exploratory.
By 2016, genome-wide association studies had identified roughly 58 loci linked to coronary artery disease, but the authors noted that the causal variant, causal gene, and direction of effect remained unknown for most of them. A 2024 review reiterated that coronary artery calcification is a hallmark of atherosclerosis and that its molecular pathways involve inflammation, lipid accumulation, and smooth muscle cell proliferation, but it offered no new trial data. A 2017 overview stated that CAD still accounts for about one third or more of deaths in people over 35, and that treatment options include medical therapy, catheter-based interventions, and bypass grafting, without reporting comparative outcomes from a single trial.
A 2022 review of chronic coronary syndrome argued that many older randomised trials comparing medical therapy with revascularisation are now outdated because they predated the routine use of statins, antiplatelet agents, and cardioprotective anti-diabetic drugs. A 1995 study followed nearly 25,000 patients who had angiography between 1974 and 1979 and reported long-term outcomes of left main coronary surgery versus medical therapy, but the abstract gave no numerical results. What is still missing is a contemporary randomised trial that tests a repurposed drug against modern background therapy, with adequate sample size and long enough follow-up to capture hard endpoints, and that stratifies patients by the specific molecular or genetic markers identified in the expression and GWAS studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Physiological Genomics · 2003 · 95 citations
Identification of new genes differentially expressed in coronary artery disease by expression profiling
AbstractGenetic factors increase the risk to coronary artery disease (CAD). To date, a limited number of genes that potentially contribute to development of CAD have been identified. In this study, we have performed large-scale gene expression analysis of approximately 12,000 human genes in nine severely atherosclerotic and six nonatherosclerotic human coronary arteries using oligonucleotide microarrays. Fifty-six genes showed differential expression in atherosclerotic coronary artery tissues; expression of 55 genes was increased in atherosclerotic coronary arteries, whereas only one gene, GST, encoding a reducing agent, showed downregulated expression. The expression data of selected genes were validated by quantitative RT-PCR analysis as well as immunostaining. The associations of 49 genes with CAD appear to be novel, and they include genes encoding ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, beta2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-alpha-induced protein 2 (B94), and flavocytochrome 558. In conclusion, we have identified 56 genes whose expression is associated with CAD, and 49 of them may represent new genes linked to CAD.
Circulation Research · 2016 · 59 citations · open access
From Loci to Biology
AbstractGenome-wide association studies have provided a rich collection of ≈ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are several tools that can be used for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci, and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.
Deutsches Ärzteblatt international · 2014 · 18 citations · open access
The Effects of Theophylline on Hospital Admissions and Exacerbations in COPD Patients
AbstractBACKGROUND: Theophylline is often used to treat chronic obstructive pulmonary disease (COPD). Current evidence leaves the effectiveness and safety of this drug open to question. Thus, we evaluated the effectiveness of theophylline on the rate of hospitalizations and disease exacerbations by examining routine data from the ambulatory disease management program for COPD in the German state of Bavaria. METHOD: Data sets from a total of 30 330 patients were examined. Logistic regression models were used to calculate propensity scores that controlled for baseline characteristics. These propensity scores, in turn, were used to create comparable patient groups, which were observed for a median follow-up time of 9 quarters (the theophylline group) and 10 quarters (the control group). RESULTS: 1496 patients with first prescription of theophylline were matched with 1496 patients with no record of theophylline treatment. 1. The probability of suffering an exacerbation during the period of observation, was 33.5% for the control group and 43.4% for the theophylline group [hazard ratio (HR) 1.41; 95% confidence interval (CI) 1.24 to 1.60], yielding a number needed to harm (NNH) of 11 (95% CI 7.7 to 20.9). The probability for hospitalization was 11.4% for the control group and 17.4% of the theophylline group (HR 1.61; 95% CI 1.29 to 2.01), yielding a NNH of 17 (95%CI 11.0-34.5). CONCLUSION: Treatment with theophylline is associated with an elevated incidence of exacerbations and hospitalizations. The therapeutic value of this drug should be reconsidered and investigated in further studies.
Journal of Clinical Medicine · 2024 · 10 citations · open access
From Cells to Plaques: The Molecular Pathways of Coronary Artery Calcification and Disease
AbstractCoronary artery calcification (CAC) is a hallmark of atherosclerosis and a critical factor in the development and progression of coronary artery disease (CAD). This review aims to address the complex pathophysiological mechanisms underlying CAC and its relationship with CAD. We examine the cellular and molecular processes that drive the formation of calcified plaques, highlighting the roles of inflammation, lipid accumulation, and smooth muscle cell proliferation. Additionally, we explore the genetic and environmental factors that contribute to the heterogeneity in CAC and CAD presentation among individuals. Understanding these intricate mechanisms is essential for developing targeted therapeutic strategies and improving diagnostic accuracy. By integrating current research findings, this review provides a comprehensive overview of the pathways linking CAC to CAD, offering insights into potential interventions to mitigate the burden of these interrelated conditions.
Abstract<h3>To the Editor.—</h3> The report by Keltz et al<sup>1</sup>linking oral dipyridamole to myocardial ischemia deserves comment. In my opinion, the clinical information provided does not allow for the conclusion that dipyridamole was the cause of the ischemic episodes. The significance of the one reported case of myocardial infarction with a fatal outcome cannot be determined on the basis of the authors' small series of patients without comparison to a control group. To elucidate further the incidence of myocardial infarction and coronary death resulting from dipyridamole administration, I examined adverseevent data from two large studies of patients treated with dipyridamole (Persantine). In an ongoing multicenter, randomized, double-blind, placebo-controlled study of patients undergoing coronary artery bypass graft surgery, dipyridamole was given at a dosage of 100 mg four times daily for two days preoperatively and continued thereafter. Myocardial infarction and/or coronary death occurred preoperatively in 0.4% (1/259) of the patients
Medical and Surgical Management and Outcomes for Coronary Artery Disease
AbstractCoronary artery disease (CAD) is a major cause of death and disability in developed countries. Although coronary artery disease mortality rates worldwide have declined over the past decades, CAD remains responsible for about one third or more of all deaths in individuals over the age of 35 years. Various methods of treatment have been proposed including medical therapy, catheter-based interventions, and lastly, coronary artery bypass grafting. The purpose of this chapter is to outline those treatment regimens and examine the literature detailing their outcomes in hopes of guiding treatment.
International Journal of Cardiovascular Sciences · 2022 · 1 citations · open access
Chronic Coronary Syndrome: Medical Therapy or Myocardial Revascularization?
AbstractThe best therapeutic strategy for chronic coronary syndrome (CCS) is still controversial. The lack of contemporaneity of medical treatment in many randomized clinical trials prior to the large-scale use of statins, antiplatelet agents, anti-diabetic drugs with cardiovascular protection, and changes in life habits with well-established goals limits the applicability of such studies in current clinical practice. Medical treatment is the only therapeutic option capable of reducing atherosclerotic damage and, therefore, of acting effectively in preventing the progression of this [...]
AbstractMost studies that measure the relative benefits of surgery versus medical therapy for coronary artery disease compare outcomes after a few years at most. These investigators followed nearly 25,000 patients who underwent coronary angiography at 15 hospitals in North America between 1974 and 1979; they present the long-term outcomes of patients with …
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.
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