DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for congestive heart failure — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongestive heart failure maps to a 46-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 congestive heart failure 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 the orphan nuclear receptor ROR(gamma)t ligand-binding domain — Digoxin has a real, experimentally solved structure in complex with this target (PDB 3B0W, 2.2 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 dgxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3B0W · 2.2 Å · ligand Digoxin (DGX). Experimental structure, not a prediction.
What the evidence adds up to
Congestive heart failure remains a common clinical problem with significant morbidity and mortality, and a clear tendency toward increasing numbers of patients, high hospitalisation rates during decompensation, and high mortality. Despite decades of research, the detailed molecular mechanisms of heart failure remain elusive because of the disease's complexity, which has hindered the development of new intervention approaches. Chronic heart failure treatment has improved patient prognosis and survival, but the therapeutic management of acute heart failure has remained virtually unchanged in the last several decades.
Recent data have linked cardiac hypertrophy, aberrant signalling, and cytoskeletal abnormalities to the development of heart failure, confirming the importance of many classical pathways while also revealing novel ones. The pathological mechanisms through which cardiovascular diseases result in heart failure include myocardial fibrosis and hypertrophy, myocardial cell death, mitochondrial dysfunction, vascular remodelling, and calcium dysregulation. However, these findings come from reviews and scientific statements that summarise existing knowledge rather than from new experimental or clinical trials testing a specific drug.
The scarcity of pre-clinical models for the pathophysiological assessment of acute heart failure is cited as a reason for limited knowledge of the molecular mechanisms involved in different acute heart failure phenotypes. The interaction between aetiology, genetic and environmental factors, and comorbidities determines trajectories from acute to chronic heart failure. Potential molecular targets are discussed as capable of unveiling new therapeutic perspectives, but no concrete drug, survival data, response rates, or sample sizes from a clinical trial are reported in any of these abstracts.
What is still missing is a specific, tested drug candidate with published clinical outcomes in heart failure patients. The field lacks adequately funded pre-clinical models that reflect acute heart failure phenotypes, and the detailed molecular mechanisms remain too poorly understood to guide rational drug repurposing. No patient stratification strategy based on molecular subtypes has been validated in a trial setting.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2001 · 3100 citations · open access
Effect of Carvedilol on Survival in Severe Chronic Heart Failure
AbstractBACKGROUND: Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure. METHODS: We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention, or were receiving intravenous vasodilators or positive inotropic drugs were excluded. RESULTS: There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected a 35 percent decrease in the risk of death with carvedilol (95 percent confidence interval, 19 to 48 percent; P=0.00013, unadjusted; P=0.0014, adjusted for interim analyses). A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol (95 percent confidence interval, 13 to 33 percent; P<0.001). The favorable effects on both end points were seen consistently in all the subgroups we examined, including patients with a history of recent or recurrent cardiac decompensation. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (P=0.02). CONCLUSIONS: The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.
Cleveland Clinic Journal of Medicine · 2006 · 27 citations
Is digoxin a drug of the past?
AbstractDigoxin has been the cornerstone of the treatment of heart failure for more than 2 centuries. Now that newer therapies have been introduced that reduce the mortality rate in heart failure and recent trials have failed to prove the same for digoxin, its use has significantly decreased. But a careful review of the multiple pharmacologic actions of digoxin and closer analysis of the results of recent trials suggest that digoxin may in fact continue to be an effective treatment for heart failure.
Current Opinion in Cardiology · 2000 · 26 citations
Advances in the molecular mechanisms of heart failure
AbstractCongestive heart failure is a common clinical problem resulting in significant morbidity and mortality. Although considerable progress has been made in elucidating the pathophysiologic mechanisms that lead to the development of this process, much remains unknown. The techniques of modern molecular biology now allow a detailed and systematic analysis of this disease. Recent data linking cardiac hypertrophy, aberrant signaling, or cytoskeletal abnormalities to the development of heart failure have provided new insights into this process. These studies have confirmed the importance of many classical pathways but also revealed novel pathways. This review will focus on the recent advances that have been made and will highlight the importance they have had in our understanding and treatment of heart failure.
International Journal of Molecular Medicine · 2025 · 12 citations · open access
Molecular mechanisms and intervention approaches of heart failure (Review)
AbstractHeart failure is a major health issue that threatens life and health. Previous studies have shown that heart failure is the terminal stage of arrhythmia, dilated cardiomyopathy, hypertension, hypertrophic cardiomyopathy and myocardial infarction. The pathological mechanisms through which cardiovascular diseases result in heart failure include myocardial fibrosis and hypertrophy, myocardial cell death, mitochondrial dysfunction, vascular remodeling and calcium dysregulation. However, the detailed molecular mechanisms of heart failure remain elusive because of its complexity, hindering the development of intervention approaches for heart failure. The present study reviewed recent research progress on heart failure and provided references and strategies for the prevention and treatment of heart failure.
Cardiovascular Research · 2023 · 8 citations · open access
Acute heart failure: mechanisms and pre-clinical models—a Scientific Statement of the ESC Working Group on Myocardial Function
AbstractWhile chronic heart failure (CHF) treatment has considerably improved patient prognosis and survival, the therapeutic management of acute heart failure (AHF) has remained virtually unchanged in the last decades. This is partly due to the scarcity of pre-clinical models for the pathophysiological assessment and, consequently, the limited knowledge of molecular mechanisms involved in the different AHF phenotypes. This scientific statement outlines the different trajectories from acute to CHF originating from the interaction between aetiology, genetic and environmental factors, and comorbidities. Furthermore, we discuss the potential molecular targets capable of unveiling new therapeutic perspectives to improve the outcome of the acute phase and counteracting the evolution towards CHF.
ACETYLDIGITOXIN IN THERAPY OF AMBULATORY PATIENTS WITH CONGESTIVE HEART FAILURE
Abstract• Dosages of acetyldigitoxin required for initial digitalization and for subsequent maintenance were determined by oral administration of the drug to ambulatory adult patients with congestive heart failure of recent onset. The digitalizing dose as determined in 31 patients ranged from 0.8 mg. in 24 hours to 3.2 mg. in 120 hours or more and averaged 1.6 to 2.0 mg. in 48 to 72 hours. The drug was usually given in doses of 0.2 mg. three or four times a day. The maintenance dose was determined in 38 patients and was found to range from 0.05 to 0.2 mg. per day. Acetyldigitoxin was shown to be a useful form of digitalis on the basis of margin of safety, rapid reversibility of toxic manifestations, and effectiveness in ambulatory patients with congestive heart failure.
Современное представление о распространенности хронической сердечной недостаточности
AbstractCongestive heart failure (CHF) is one of the main problems of public health. There is an obvious tendency to increase in the number of patients with CHF, and a high level of hospitalization in decompensation of the disease and mortality. The review considers the prevalence as a reason for a thorough study of CHF, the possibility of changes in the course, adaptation of treatment strategy and prognosis of the disease with increasing life expectancy.
Therapeutic efficacy of diuretics with different durations of action
AbstractA new assay is described for measuring, in patients with congestive heart failure, the therapeutic efficacy of diuretics such as polythiazide, which was shown to have a longer duration of action than hydrochlorothiazide. In terms of weight loss over 1-week periods of therapy with maximal doses of diuretics, there was no significant difference in the activity of hydrochlorothiazide and polythiazide. A prolonged effect on renal sodium excretion, therefore, is not necessarily associated with an improvement in net therapeutic efficacy when these drugs are used in the management of fluid retention secondary to congestive heart failure.
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.
