DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for Prinzmetal's angina — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePrinzmetal's angina maps to a 4-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 prinzmetal's angina in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
CYP2C8dH — Felodipine has a real, experimentally solved structure in complex with this target (PDB 2NNJ, 2.28 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 225drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2NNJ · 2.28 Å · ligand Felodipine (225). Experimental structure, not a prediction.
What the evidence adds up to
Prinzmetal angina is defined by episodes of chest pain at rest with ST-segment changes, now understood as coronary vasospasm rather than fixed coronary artery disease. A 2021 case report notes that diagnosis is especially challenging in patients who have already had percutaneous coronary interventions. A 2022 review states that a third of patients still have angina symptoms despite recent progress in understanding pathogenetic mechanisms and developing new treatment strategies. The same review calls Prinzmetal angina a multifactorial malignant dysregulation of coronary artery tone with a high risk of cardiovascular complications and sudden death.
A 1975 letter reports that in literature reviews, the incidence of myocardial infarction in Prinzmetal angina was 25% and 24%, and the incidence of sudden death was 15% and 14%. Five additional deaths in medically treated patients were reported at that time. The letter states that the prognosis of patients with Prinzmetal angina remains guarded.
No drug is mentioned in any of these abstracts. No controlled trial data, no response rates, no survival benefit from any intervention is reported. What is still missing is a randomised trial design that can test treatments specifically in the vasospastic subtype, adequate funding for such trials, and a method to stratify patients by whether spasm occurs on normal or diseased coronary arteries.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Japanese Circulation Journal-english Edition · 1978 · 96 citations · open access
Pathogenesis and treatment of angina pectoris at rest as seen from its response to various drugs.
AbstractTo twenty six patients with angina at rest (including 13 patients with Prinzmetal's variant angina), propranolol 40--50 mg, dilitiazem 60--90 mg, dipyridamole 50 mg, atropine sulfate 0.6 mg and phenoxybenzamine 10--20 mg were given at 9:00 p.m. and 2:00 a.m. (except phenoxybenzamine which was given only at 9:00 p.m.) to examine the effect of these drugs on the attack. Propranolol was not only ineffective in suppressing the attack but rather tended to aggravate it in all the cases of Prinzmetal's variant angina. It was effective to some degree in 5 of 13 cases of angina at rest other than Prinzmetal's variant angina. Diltiazem suppressed the attack completely and dramatically in all the cases of angina at rest (including Prinzmetal's variant angina). Dipyridamole was ineffective in all the cases except one in suppressing the attack. Atropine sulfate and phenoxybenzamine suppressed the attack in 13 of 21 cases and in 6 of 12 cases respectively. Coronary arteriography was done before and after the intravenous administration of 10 mg of diltiazem in 8 patients and it was demonstrated that diltiazem dilates large coronary arteries in all these patients. It is concluded that diltiazem, a calcium antagonistic drug, is specifically effective in suppressing the attack of angina at rest by dilating large coronary arteries and that the autonomic nervous system plays a role in the genesis of the attack probably by constricting large coronary arteries by way of alpha adrenergic receptors.
Cochrane Database of Systematic Reviews · 2017 · 92 citations · open access
Trimetazidine for stable angina
AbstractBACKGROUND: Patients with stable angina not controlled by monotherapy with nitrates, beta blockers, or calcium channel blockers are often treated with combinations of these drugs. There may be adverse effects from, or contraindications to, the use of combinations. In low risk groups, medical treatment appears to be as good an option as percutaneous transluminal coronary angioplasty in terms of averting myocardial infarction, death, or subsequent revascularization. Revascularization procedures are too costly or inaccessible for many patients in developing countries therefore effective and safe medical treatment is needed. Trimetazidine is a less well known anti-anginal drug that controls myocardial ischaemia through intracellular metabolic changes. Trimetazidine has been reported, in some studies, to be better tolerated than combined anti-anginal therapy; however it is not considered in published guidelines. OBJECTIVES: To determine the efficacy and tolerability of trimetazidine in patients with stable angina. SEARCH METHODS: We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS and SCISEARCH, without language restriction, from inception to October 2003. Experts in the field were contacted to locate unpublished studies. SELECTION CRITERIA: Randomised studies comparing trimetazidine with placebo, or other anti-angina drug in adults with stable angina. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted data. MAIN RESULTS: Twenty-three studies (1378 patients) met the inclusion criteria. There was a paucity of information about mortality, cardiovascular events and quality of life. Trimetazidine, compared with placebo, reduced the number of weekly angina attacks ( mean difference -1.44, 95% CI -2.10 to -0.79; P < 0.0001), reduced weekly nitroglycerin tablet consumption (95% CI -1.47 to -2.20, -0.73; P < 0.0001) and improved exercise time to 1 mm segment depression (P = 0.0002). Four small trials (263 patients) compared trimetazidine against other anti-anginal agents. One favoured trimetazidine over nitrates. Three tended to favour alternative regimens but with confidence intervals consistent with both major increases and decreases in frequency of angina episodes. In this subgroup, adverse events were considered in 5 trials (448 patients) and totals of 2 versus 12 drop outs due to adverse events were observed in the trimetazidine and alternative regimens respectively, but this was mostly driven by a single trial. AUTHORS' CONCLUSIONS: Trimetazidine is effective in the treatment of stable angina compared with placebo, alone or combined with conventional anti-anginal agents. Trimetazidine may result in fewer dropouts due to adverse events. Large, long term trials comparing trimetazidine with other anti-anginal drugs assessing clinically relevant important outcomes are required to establish its role in clinical management.
Verapamil Administration in Variant Angina Pectoris
AbstractSix patients with Prinzmetal's variant angina were treated with oral verapamil administration. Before and after the initiation of therapy, ambulatory ECG monitoring was performed to assess objectively the response to therapy. With verapamil administration, the frequency of both chest pain and transient ST-segment deviations was sharply diminished. (<i>JAMA</i>1981;245:1849-1851)
The effects of treatment with felodipine as a single agent in coronary artery disease.
AbstractIn an earlier study one dose of the vasodilator felodipine improved haemodynamic function in patients with angina without having a negative inotropic effect. The haemodynamic response of sustained treatment with felodipine as a single agent in stable angina was investigated in a double blind crossover study of 25 patients. The dosage of felodipine was increased from 5 mg twice daily to 10 mg twice daily after two weeks. Twenty one patients completed the study, two were withdrawn because of acute myocardial infarction, and a further two because of symptoms of vasodilatation. Felodipine reduced both supine and erect blood pressure and increased the resting heart rate. Median exercise time was increased by 10% at two weeks and 7% at four weeks. There was a sustained reduction in the number of angina attacks and use of sublingual nitrate on active treatment. Felodipine has antianginal effects but these are limited and seem less than those of other related compounds. This finding is unexpected and possibly related to increased heart rate.
Journal of Transcatheter Interventions · 2021 · 2 citations · open access
Prinzmetal angina in a patient with previous coronary artery disease.Topic review and case report
AbstractPrinzmetal angina is described as episodes of chest pain that occur at rest, associated with electrocardiographic changes in the ST-segment, which may or may not evolve to ischemia, and are not caused by coronary artery disease, having more recently been related to a coronary vasospasm. This diagnosis becomes especially challenging in patients who have already undergone previous percutaneous coronary procedures. We report a case of a patient diagnosed with Prinzmetal angina with a recent percutaneous coronary intervention due to coronary artery disease.
AbstractPrinzmetal angina is a multifactorial malignant dysregulation of coronary artery tone with a high risk of cardiovascular complications and sudden death. Timely diagnosis and treatment of this disease allow to stabilize the patient condition. Despite the recent progress in the study of pathogenetic mechanisms and in the development of new treatment strategies, a third of patients still have angina symptoms, which requires further research in this area in order to improve the life quality and prognosis in this disease.
Archives of Internal Medicine · 1975 · 0 citations
Prinzmetal Angina
Abstract<h3>To the Editor.</h3> —We thank Drs Adyanthaya and Gaasch for their comments in theArchives(135:747,1975) on our paper on Prinzmetal angina,<sup>1</sup>and we welcome the opportunity to restate our position in the light of more recent contributions. The high incidence (usually short-term) of myocardial infarction and sudden death in Prinzmetal angina has been reported in the literature reviews by both McAlpin et al<sup>2</sup>and us<sup>1</sup>as 25% and 24%, respectively, for myocardial infarction, and 15% and 14%, respectively, for sudden death. Five additional deaths have been reported recently in medically treated patients.<sup>3-5</sup>The prognosis of patients with Prinzmetal angina remains guarded; hence, the surgical approach is appealing in principle. The distinctive feature of Prinzmetal angina is the occurrence of spasm of the coronary arteries. Spasm may develop in an angiographically normal vessel or be superimposed on a subcritical or critical organic constriction. Our paper was
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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