DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for hypertension — 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 moduleHypertension 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 hypertension in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Endothiapepsin — Norepinephrine has a real, experimentally solved structure in complex with this target (PDB 4Y4J, 1.03 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 lnrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Y4J · 1.03 Å · ligand Norepinephrine (LNR). Experimental structure, not a prediction.
What the evidence adds up to
The adrenal transcriptome of stress-sensitive hypertensive ISIAH rats shows multiple differentially expressed genes compared to normotensive WAG rats. Candidate genes include transcription factors Nr4a3 and Ppard, which may relate to sympathetic-adrenal medullary activation, and Avpr1a, Hsd11b2, Agt, Ephx2, which may provoke hypertension development, while Mpo may contribute to insulin resistance and inflammation. The authors note the complex nature of stress-sensitive hypertension pathogenesis and suggest these data may be useful for identifying potential therapeutic targets, but no drug was tested in this study.
Stevia leaf extracts, steviol glycosides, and stevia leaf protein hydrolysates inhibited angiotensin-converting enzyme activity by 26.60%, 59.56%, and 74.38% respectively in vitro, with dose-dependent effects. The authors claim this inhibition is superior to pharmaceutical drugs, but no direct comparator drug was tested in the same assay. An animal test in spontaneously hypertensive rats showed a significantly antihypertensive effect, but no human data are provided. The sample size, duration, and magnitude of blood pressure reduction in rats are not reported in the abstract.
A review of genetic hypertension research from 2003 to 2004 notes that the renin-angiotensin-aldosterone system dominates investigation, but data on gene-gene and gene-environment interactions are sparse. The review concludes that how candidate genes fit into the pathophysiological network remains unclear and that advanced tools like transcriptomics and proteomics are underused. A separate clinical review states that true refractory hypertension is unusual and that proper adjustment of drug doses, including effective use of diuretics, often restores blood pressure; hydralazine or minoxidil may be considered for some patients.
A Korean cohort study of 40,496 patients with uncomplicated hypertension (excluding heart failure, coronary artery disease, stroke, malignancy, diabetes, or chronic kidney disease) found that treatment from baseline was associated with a hazard ratio of 0.49 for all-cause mortality and 0.62 for cardiovascular mortality compared to never-treated patients. Treatment started during follow-up gave hazard ratios of 0.41 and 0.44 respectively. Among drug classes, renin-angiotensin system blockers and calcium channel blockers were associated with lower all-cause mortality, but only calcium channel blockers were associated with lower cardiovascular mortality on multivariable analysis. What remains missing is prospective randomised trial data in uncomplicated hypertension, consistent patient stratification by genetic or molecular subtypes, and funding for translational work that moves animal transcriptome findings or in vitro ACE inhibition into human clinical testing.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Critical Care Medicine · 1994 · 185 citations
High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs
AbstractOBJECTIVE: To determine whether high-dose epinephrine (0.2 mg/kg) during cardiopulmonary resuscitation (CPR) results in improved outcome, compared with standard-dose epinephrine (0.02 mg/kg). DESIGN: A prospective, randomized, blinded study. SETTING: Research laboratory of a university medical center. SUBJECTS AND INTERVENTIONS: Thirty domestic swine were randomized to receive standard- or high-dose epinephrine during CPR after 15 mins of fibrillatory cardiac arrest. Three minutes of CPR were provided, followed by advanced cardiac life support per American Heart Association guidelines. Animals that were successfully resuscitated were supported for 2 hrs in an intensive care unit (ICU) setting, and then observed for 24 hrs. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram, aortic blood pressure, right atrial blood pressure, and end-tidal CO2 were monitored continuously until the intensive care period ended. Survival and neurologic outcome were determined. Return of spontaneous circulation was attained in 14 of 15 animals in each group. Four of 14 high-dose epinephrine pigs died during the ICU period after return of spontaneous circulation vs. zero of the 14 standard-dose pigs (p < .05). Six standard-dose pigs survived 24 hrs vs. four high-dose pigs. Twenty-four-hour survival rate and neurologic outcome were not significantly different. Within 10 mins of defibrillation, severe hypertension (diastolic pressure > 120 mmHg) occurred in 12 of 14 high-dose pigs vs. two of 14 standard-dose pigs (p < .01). Severe tachycardia (heart rate > 250 beats/min) occurred in seven of 14 high-dose pigs vs. zero of 14 standard-dose pigs (p < .01). All four high-dose epinephrine pigs that died during the ICU period experienced both severe hypertension and tachycardia immediately postresuscitation. CONCLUSIONS: High-dose epinephrine did not improve 24-hr survival rate or neurologic outcome. Immediately after return of spontaneous circulation, most animals in the high-dose epinephrine group exhibited a hyperadrenergic state that included severe hypertension and tachycardia. High-dose epinephrine resulted in a greater early mortality rate.
Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats
AbstractBACKGROUND: The adrenals are known as an important link in pathogenesis of arterial hypertensive disease. The study was directed to the adrenal transcriptome analysis in ISIAH rats with stress-sensitive arterial hypertension and predominant involvement in pathogenesis of the hypothalamic-pituitary-adrenal and sympathoadrenal systems. RESULTS: The RNA-Seq approach was used to perform the comparative adrenal transcriptome profiling in hypertensive ISIAH and normotensive WAG rats. Multiple differentially expressed genes (DEGs) related to different biological processes and metabolic pathways were detected. The discussion of the results helped to prioritize the several DEGs as the promising candidates for further studies of the genetic background underlying the stress-sensitive hypertension development in the ISIAH rats. Two of these were transcription factor genes (Nr4a3 and Ppard), which may be related to the predominant activation of the sympathetic-adrenal medullary axis in ISIAH rats. The other genes are known as associated with hypertension and were defined in the current study as DEGs making the most significant contribution to the inter-strain differences. Four of them (Avpr1a, Hsd11b2, Agt, Ephx2) may provoke the hypertension development, and Mpo may contribute to insulin resistance and inflammation in the ISIAH rats. CONCLUSIONS: The study strongly highlighted the complex nature of the pathogenesis of stress-sensitive hypertension. The data obtained may be useful for identifying the common molecular determinants in different animal models of arterial hypertension, which may be potentially used as therapeutic targets for pharmacological intervention.
Angiotensin-converting enzyme inhibiting ability of ethanol extracts, steviol glycosides and protein hydrolysates from stevia leaves
AbstractEfficient treatment of hypertension is vital. The inhibition of angiotensin-converting enzyme activity has been one of the major strategies for treating hypertension. The ethanol extract of stevia leaves, steviol glycosides (with 95% purity; natural sweeteners widely used in the food industry) isolated from the ethanol extract and stevia leaf protein hydrolysates inhibited 26.60%, 59.56% and 74.38% of angiotensin-converting enzyme activities, respectively. Their effect was dose-dependent, which can be beneficial for avoiding hypertension or hypotension just by the proper control of the amount of their intake, and it was found to be superior to that of pharmaceutical drugs. A sensory test indicated that the application of the mixtures of steviol glycosides and stevia protein hydrolysates to decaffeinated coffee or tea as well as a formulated peanut protein drink was found to be well accepted, and an animal test showed that they had a significantly antihypertensive effect in spontaneously hypertensive rats. Steviol glycosides and stevia leaf protein hydrolysates can be good ingredients for making functional or healthy food products or beverages targeted for the prevention or treatment of hypertension.
Pressor response to norepinephrine in essential hypertension. A study in families.
AbstractStudy of pressor response to graded, increased doses of infused norepinephrine in patients with essential hypertension, their normotensive siblings, and normotensive control subjects unrelated to the patients and without a family history of hypertension indicated an increased response in the two former groups. Comparison of the dose-response curves in the three groups showed that the difference in response was due to a reduced threshold to norepinephrine in patients and their siblings and not to differences in the slopes of the dose-response curves. These alterations were not paralleled by differences in heart rate responses.
Current Opinion in Nephrology & Hypertension · 2005 · 14 citations
The search for the genetic basis of hypertension
AbstractPURPOSE OF REVIEW: This review surveys the literature on the search for the genetic basis of hypertension during the 10 months since November 2003. The goals set forth by this search are defined and the highlights of the work accomplished are provided. RECENT FINDINGS: The search for the genetic basis of hypertension is ongoing, generating an abundance of new data. These data consist of a large number of candidate genes, association of previously known and novel candidate genes with various facets of hypertension, detection of new quantitative trait loci and identification of genes that mediate susceptibility to hypertension. The renin-zangiotensin-aldosterone system continues to dominate the interest of investigators. Other gene systems are also emerging but a single-gene system cannot be singled out beyond the renin-angiotensin-aldosterone system and the data are mostly sporadic and do not reflect a guided or coordinated effort to resolve unanswered issues. The notion that hypertension is polygenic is reinforced, yet few data are provided as to the actual number of genes involved, gene-gene interaction or gene-environment interaction. Advanced biotechnological tools involving transcriptomics and proteomics are underused. SUMMARY: Research on the genetic basis of hypertension has generated over the past year a large number of candidate genes and tied them to various aspects of hypertension. How these genes fit into the complex pathophysiological network that induces hypertension remains unclear. The task of putting together these genes into a cohesive framework still lies ahead, but promises to enlighten us as to the true nature of hypertension, the pathogenic mechanisms involved and improved therapeutic and preventive measures.
American Journal of Therapeutics · 2003 · 9 citations
Management of Refractory Hypertension
AbstractTrue refractory hypertension is unusual in clinical practice, thanks to the widespread availability of antihypertensive drugs and national mandate to optimize blood pressure control levels in the community. However, at times the blood pressure may become refractory to initial drug therapy. When the blood pressure levels do not reach a target level despite usual therapy, hypertension is considered refractory. There should be proper evaluation of such patients to determine the factor(s) responsible for resistance to therapy. In many patients, proper adjustment of drug doses, including effective use of diuretics, restores the blood pressure level. For some patients, potent drug therapy, such as hydralazine or minoxidil, must be considered. Based upon clinical course, work-up for secondary causes of hypertension should be considered in selected patients. Refractory hypertension requires proper analysis of etiologic factors and consideration of rational drug selection, and at times, work-up for secondary causes of hypertension.
Journal of Hypertension · 2017 · 2 citations · open access
Treatment of uncomplicated hypertension is associated with a reduction in cardiovascular mortality
AbstractBACKGROUND: Although the benefit of hypertension treatment is well established in high-risk patients, there is a paucity of evidence regarding the benefit of treatment in patients with uncomplicated hypertension. METHODS: Hypertensive adult patients were selected from the Korea National Health Insurance Sample Cohort in 2002 and were followed until 2013. Patients with a diagnosis of heart failure, coronary artery disease, stroke, malignancy, diabetes, or chronic kidney disease were excluded. Ultimately, 40 496 patients were divided into three groups: never-treated (N = 6756), treated-from-baseline (N = 28 443), and treated-during-follow-up (N = 5297). Five first-line antihypertensive agents were categorized into four classes: renin-angiotensin system blocker (RASB), beta-blocker, calcium channel blocker (CCB), and diuretics. All-cause mortality, cardiovascular mortality, and hazard ratio were determined. RESULTS: All-cause and cardiovascular mortality rates were significantly lower in both treatment groups than in the never-treated group (all log-rank P < 0.001). Treatment from baseline (hazard ratio = 0.49 for all-cause mortality and hazard ratio = 0.62 for cardiovascular mortality) and treatment started during follow-up (hazard ratio = 0.41 for all-cause mortality and hazard ratio = 0.44 for cardiovascular mortality) were independently associated with lower mortality on multivariable Cox analyses. Although RASB, beta-blocker, and CCB significantly reduced all-cause mortality, multivariable Cox analyses showed that RASB and CCB were closely associated with lower all-cause mortality. In terms of cardiovascular mortality, only CCB was associated with lower cardiovascular mortality on multivariable Cox analyses. CONCLUSION: Treatment of hypertension significantly reduces mortality in patients with uncomplicated hypertension.
Ginekologia Polska · 2024 · 2 citations · open access
Effects of intravenous nicardipine followed by oral labetalol in combination with nifedipine controlled-release tablet on severe peripartum hypertension
AbstractOBJECTIVES: To investigate the effects of intravenous nicardipine as initial therapy and oral labetalol combined with nifedipine controlled-release tablet as subsequent treatment of severe peripartum hypertension. MATERIAL AND METHODS: Intravenous nicardipine was delivered as the initial treatment, after the target blood pressure (BP) had been achieved, oral labetalol was used to maintain the target BP. If oral labetalol failed to maintain the target BP, oral labetalol combined with nifedipine controlled-release tablet was used. RESULTS: A total number of 131 patients were enrolled. The target BP (BP < 140/90 mmHg) was achieved in all patients within 60 minutes by intravenous nicardipine. After receiving labetalol orally, the target BP was maintained in nine patients. However, in 104 patients, we had to combine oral labetalol and nifedipine controlled-release tablet due to re-elevation of their systolic BP to 140-159 mmHg. In 18 patients, we restarted intravenous nicardipine because their systolic BP re-elevated above 160 mm Hg. Among the 104 patients who received oral labetalol and nifedipine controlled-release tablet, the target BP was achieved and maintained in 96 patients, and eight patients had to restart nicardipine. Of the total number of 26 patients in whom intravenous nicardipine was resumed, the target BP was successfully maintained in 22 patients with oral labetalol combined with nifedipine controlled-release tablet. CONCLUSIONS: Intravenous nicardipine rapidly and safely lowered severe peripartum hypertension. As subsequent therapy, oral labetalol combined with nifedipine controlled-release tablet protocol may be applied to effectively maintain a target BP.
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.
