DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for systolic heart failure — screening already-approved drugs against its 22-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSystolic heart failure maps to a 22-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 systolic 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 Aspergillus fumigatus chitinase B1 — Theophylline has a real, experimentally solved structure in complex with this target (PDB 2A3A, 2.1 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.
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RCSB Protein Data Bank · entry 2A3A · 2.1 Å · ligand Theophylline (TEP). Experimental structure, not a prediction.
What the evidence adds up to
The 2020 review states that evidence-based treatment options exist only for heart failure with a low ejection fraction, and that pharmacotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis has been further improved by the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Implantable defibrillators and pacemakers for cardiac resynchronisation are well established, while the utility of baroreflex modulation or cardiac contractility modulation needs further study. Catheter-based treatment of secondary mitral regurgitation with a MitraClip improved the outcome of selected patients.
The 2010 review confirms that angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and beta blockers have demonstrated prognostic benefit in a large body of clinical trials. An aldosterone antagonist and/or a digitalis glycoside may provide additional benefit depending on disease stage and concomitant factors. Most patients also receive a diuretic for symptomatic relief. The 2005 review notes that heart failure affects over 5 million patients annually, with 400,000 to 700,000 new cases each year, and that management has changed significantly over the preceding decade. The 2014 review reiterates that angiotensin-converting enzyme inhibitors and beta-blockers are the main therapies, usually used simultaneously because of their complementary mechanism and effect, and that current guidelines limit recommended drugs to those successfully tested in large randomised trials.
No abstract reports a trial of a repurposed drug for systolic heart failure. All four abstracts describe the established standard of care: neurohormonal blockade with ACE inhibitors, ARBs, beta blockers, aldosterone antagonists, and neprilysin inhibitors, plus devices. What is still missing is any randomised evidence for a drug repurposed from another indication, a trial design that tests a novel agent against this background therapy, and patient stratification beyond ejection fraction to identify who might benefit from a new approach.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Deutsches Ärzteblatt international · 2020 · 62 citations · open access
The Treatment of Heart Failure with Reduced Ejection Fraction
AbstractBACKGROUND: Chronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death. METHODS: This review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines. RESULTS: Evidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients. CONCLUSION: The treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.
Differential Effects of Theophylline on Sympathetic Excitation, Hemodynamics, and Breathing in Congestive Heart Failure
AbstractBACKGROUND: Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known. METHODS AND RESULTS: Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO2 in the control subjects but only lowered transcutaneous CO2 in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects (P<0.01) and the heart failure patients (P<0.02). CONCLUSIONS: Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.
THE DIET AND THEOPHYLLINE IN THE TREATMENT OF CARDIAC FAILURE
AbstractThe diet and theophylline are considered together in the treatment of cardiac failure because of their related influence on the function of the heart. The diet provides the source of energy on which the heart is ultimately dependent, and the theophylline, in addition to its diuretic effect, increases the coronary circulation. This drug is most effective in the arteriosclerotic type of cardiac failure in which a defective coronary circulation is an important factor. The patient with advanced cardiac failure frequently complains of abdominal discomfort, which is often induced by a disturbed gastro-intestinal function. In those in whom the cardiac failure has extended over a long period, there may be a loss of from 20 to 30 pounds (9 to 13.6 Kg.). This means that the patient either has not received sufficient food to maintain a normal weight or has been unable to utilize it in the form provided. Under these
The Thoracic and Cardiovascular Surgeon · 2010 · 3 citations
Drug Treatment for Chronic Systolic Heart Failure
AbstractDrug treatment of chronic systolic heart failure usually includes angiotensin-converting enzyme inhibitor, or an angiotensin II receptor blocker, and a beta blocker, as prognostic benefit of these agents has been demonstrated in a large body of clinical trials. Depending on the stage of the disease and concomitant factors, an aldosterone antagonist and/or a digitalis glycoside may provide additional benefit. Most patients also receive a diuretic for symptomatic relief. Conversely, some drugs may precipitate or aggravate chronic systolic heart failure.
Emergency Medicine Australasia · 2005 · 2 citations
Management of chronic heart failure: An old disease with a new face
AbstractHeart failure is a leading cause of morbidity and mortality. It affects over 5 million patients annually. There are an estimated 400,000-700,000 new cases diagnosed each year. The management of heart failure has changed significantly over the last decade. This review focuses on the pharmacologic management of systolic heart failure, and provides current recommendations for the practicing acute care provider.
Kardiologia Polska · 2014 · 0 citations · open access
Angiotensin-converting enzyme inhibitors and beta-blockers in the treatment of symptomatic heart failure
AbstractAngiotensin-converting enzyme inhibitors and beta-blockers are the main therapies used in the treatment of symptomatic systolic heart failure. In practice, those two groups are usually used simultaneously because of their complementary mechanism and effect. Current guidelines limit the list of recommended drugs to those, that were successfully tested in large randomised trials. In addition, they provide optimal dosage that was used in these studies. This article presents a summary of the current recommendations in this topic.
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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