DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for ischemia — screening already-approved drugs against its 17-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIschemia maps to a 17-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
No approved-drug candidate for ischemia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
tubulin alpha 1b (TUBA1B) — TUBA1B is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6S8L · 1.801 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 review of prolyl hydroxylase domain inhibitors (PHDIs) in animal models of ischaemic disease reports that these small molecules upregulate hypoxia inducible factor-1α and -2α, thereby enhancing angiogenic, glycolytic, erythropoietic and anti-apoptotic pathways. The same review notes that surgical revascularisation, while effective at attenuating ischaemia, causes an initial re-entry of oxygen that generates reactive oxygen species and produces ischaemia/reperfusion injury. The review states that research on PHDs and HIFs has shown these molecules can serve as therapeutic targets, but it does not provide any human efficacy data, survival figures or response rates.
A 2010 case series describes a 'zero ischaemia' technique for laparoscopic and robotic partial nephrectomy in 15 patients, using pharmacologically induced hypotension to avoid warm ischaemia. The series included complex tumours in patients with multiple comorbidities. The authors call initial results encouraging but state that evaluation of long-term outcomes is ongoing. No survival or complication rates are given.
A 2023 review of ischaemia–reperfusion injury describes it as a cascade of complex pathological processes underlying stroke, myocardial infarction and acute renal failure. It considers both generally accepted and newly developed methods of correction but provides no quantitative results from any specific intervention. A 2007 article states that no single treatment for ischaemia/reperfusion injury is feasible and that most tested substances have been antioxidants; it describes a combined therapy in a single patient but gives no outcome data.
What is still missing is any randomised controlled trial in humans for any of the proposed pharmacological or surgical strategies. The animal-model data for PHDIs have not been translated into human survival or functional outcomes. The zero-ischaemia surgical series is too small to establish safety or efficacy. No patient stratification by ischaemia type, duration or comorbidity has been tested in a prospective trial. Funding for adequately powered human studies remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Antioxidants and Redox Signaling · 2013 · 44 citations
Molecular Mechanisms of Action and Therapeutic Uses of Pharmacological Inhibitors of HIF–Prolyl 4-Hydroxylases for Treatment of Ischemic Diseases
AbstractSIGNIFICANCE: In this review, we have discussed the efficacy and effect of small molecules that act as prolyl hydroxylase domain inhibitors (PHDIs). The use of these compounds causes upregulation of the pro-angiogenic factors and hypoxia inducible factor-1α and -2α (HIF-1α and HIF-2α) to enhance angiogenic, glycolytic, erythropoietic, and anti-apoptotic pathways in the treatment of various ischemic diseases responsible for significant morbidity and mortality in humans. RECENT ADVANCES: Sprouting of new blood vessels from the existing vasculature and surgical intervention, such as coronary bypass and stent insertion, have been shown to be effective in attenuating ischemia. However, the initial reentry of oxygen leads to the formation of reactive oxygen species that cause oxidative stress and result in ischemia/reperfusion (IR) injury. This apparent "oxygen paradox" must be resolved to combat IR injury. During hypoxia, decreased activity of PHDs initiates the accumulation and activation of HIF-1α, wherein the modulation of both PHD and HIF-1α appears as promising therapeutic targets for the pharmacological treatment of ischemic diseases. CRITICAL ISSUES: Research on PHDs and HIFs has shown that these molecules can serve as therapeutic targets for ischemic diseases by modulating glycolysis, erythropoiesis, apoptosis, and angiogenesis. Efforts are underway to identify and synthesize safer small-molecule inhibitors of PHDs that can be administered in vivo as therapy against ischemic diseases. FUTURE DIRECTIONS: This review presents a comprehensive and current account of the existing small-molecule PHDIs and their use in the treatment of ischemic diseases with a focus on the molecular mechanisms of therapeutic action in animal models.
Innovations in laparoscopic and robotic partial nephrectomy: a novel ‘zero ischemia’ technique
AbstractPURPOSE OF REVIEW: To describe a novel 'zero ischemia' technique for laparoscopic and robotic partial nephrectomy. RECENT FINDINGS: Laparoscopic partial nephrectomy has been performed in 15 patients without the need for warm ischemia by utilizing pharmalogically induced hypotension. This consecutive series includes complex tumors in patients with multiple comorbidities. Herein we describe our current practice, initial results, and several practical considerations associated with the application of this novel technique. SUMMARY: Initial results with our 'zero ischemia' technique have been encouraging. Evaluation of long-term outcomes is ongoing.
Ischemia–Reperfusion Injury: Molecular Mechanisms of Pathogenesis and Methods of Their Correction
AbstractAbstract—Ischemia–reperfusion is a cascade of complex and interrelated pathological processes underlying many human diseases, including such socially significant diseases as stroke, myocardial infarction, acute renal failure, etc. The present review considers modern ideas about the main biochemical and signal-regulatory processes in the cell under conditions of ischemia–reperfusion. Both generally accepted and newly developed ways of ischemia–reperfusion lesion correction aimed at different chains of this pathological process are considered.
Journal of Craniofacial Surgery · 2007 · 2 citations
Struggling With Ischemia Reperfusion Injury
AbstractIschemia reperfusion (I/R) injury is a complicated injury that compels either the patient or the practitioner. In the literature, there still is a debate over how to manage the injury. Typically, no single treatment is feasible. So far, numerous substances have been used as treatments and the majority of these are antioxidants. In this article, a combined therapy is implemented for a patient suffering from I/R injury.
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.
