DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperaldosteronism — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHyperaldosteronism maps to a 42-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
approvedTriamtereneAmiloride-sensitive sodium channel, ENaC blockerapprovedFludrocortisoneApproved drug
Structures already discussed alongside hyperaldosteronism 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 pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex — Triamterene has a real, experimentally solved structure in complex with this target (PDB 3JQ7, 1.8 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 dx2drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3JQ7 · 1.8 Å · ligand Triamterene (DX2). Experimental structure, not a prediction.
What the evidence adds up to
Primary hyperaldosteronism is now recognised as the most common form of secondary hypertension and has a strong correlation with cardiovascular disease. Failure to diagnose the condition has profound health consequences, but with proper identification and management a proportion of affected individuals can be surgically cured. The diagnostic pursuit is not simplistic, and an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm. These concepts have emerged across identification, diagnosis, and treatment.
A 2014 case report describes a 15-month-old girl with hypertension, severe hypokalemia, metabolic acidosis, and elevated serum aldosterone, plasma renin activity, and cortisol. Radiologic findings were compatible with neuroblastoma, and histopathological examination after mass excision confirmed that diagnosis. The authors conclude that hyperaldosteronism can present in unexpected atypical forms.
Molecular genetics work from 2013 notes that primary aldosteronism can be divided into hereditary and sporadic forms. Gene fusion of CYP11B1 and CYP11B2 is the pathogenesis of familial hyperaldosteronism type I, with different fusion positions producing different clinical manifestations. KCNJ5 gene mutation has been found in familial hyperaldosteronism type III and in sporadic primary aldosteronism, as germ line mutation and somatic mutation respectively, but it is not the only pathogenic mechanism. In animal experiments, knockout of the weak rectifier potassium channel Task1 and Task3 genes in mice produced more successful hyperaldosteronism models in recent years.
What remains missing are prospective trials that stratify patients by the specific genetic lesions now identified, and funding to test whether targeted therapies against those mechanisms can reduce the need for surgery or improve cardiovascular outcomes in the large undiagnosed population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Surgery · 1996 · 108 citations · open access
Primary Aldosteronism
AbstractSUMMARY BACKGROUND DATA: Management of primary hyperaldosteronism has undergone dramatic changes in the past 40 years. This retrospective study was carried out to review our recent surgical experience and to identify potential factors associated with postoperative persistent hypertension. METHODS: Forty-six patients who had adrenal surgery for primary hyperaldosteronism from 1983 to 1994 were included in the study. RESULTS: Periodic paralysis occurred in 12 (26%) patients. Hypertension and hypokalemia (mean serum potassium, 2.2 + 0.5 [+ standard deviation (SD) mmol/L) were present in all patients. Postural study was diagnostic in 85% (23 of 27). Computed tomography scan correctly localized the tumor in all except 1 patient, and venous sampling was performed in 11 patients. There was no operative mortality, and complications developed in six patients (13%), including one patient requiring re-exploration for hemostasis. All patients had a histologically documented adenoma. During a mean follow-up of 51 months, 34 (77%) of the 44 patients required no further antihypertensive treatment. Two patients were lost to follow-up. Age, response to spironolactone treatment, and blood pressure on discharge were risk factors identified for persistent hypertension. CONCLUSION: Primary hyperaldosteronism due to aldosterone-producing adenoma can be diagnosed and localized expeditiously, whereas surgical treatment can be performed safely. Hypokalemia may be cured by surgical treatment, although persistent hypertension, usually of a mild degree, still occurs in selected patients.
Archives of Internal Medicine · 1970 · 20 citations
A Preliminary Evaluation for Primary Aldosteronism
AbstractOral administration of 400μg of fludrocortisone acetate for three days suppresses aldosterone production in normal subjects with minimal effect on the excretion of Porter-Silber chromogens. Administration of fludrocortisone acetate to hypertensive patients with hyperaldosteronism suppressed aldosterone production into the normal range in all patients with essential hypertension and in one patient with adrenal nodular hyperplasia, but failed to do so in the patients with aldosterone-producing adenoma or nodular hyperplasia, confirmed subsequently. Administration of fludrocortisone acetate to hypertensive outpatients with hyperaldosteronism is an effective screening procedure for further evaluation of primary adrenal disease.
European Journal of Endocrinology · 1986 · 10 citations
Long-term treatment of idiopathic hyperaldosteronim using trilostane
AbstractThree patients with idiopathic hyperaldosteronism were continuously treated with trilostane, a competitive inhibitor of adrenal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH) (3 to 4 2/3 years). Trilostane, in conjunction with antihypertensive drugs, effectively decreased plasma aldosterone levels and improved hyperaldosteronism symptoms without undesirable side effects. Trilostane continued to be effective even when treatment was continuous. Rapid ACTH testing (iv bolus of 0.25 mg alpha 1-24 ACTH) was done on the day without trilostane after long-term treatment, and plasma levels of aldosterone and cortisol were compared to those obtained during a pre-treatment period. Results suggest that the inhibitory effect of trilostane on steroid biosynthesis rapidly disappears following discontinuance of trilostane administration even after long-term treatment, and that continuous treatment causes no significant or irreversible change in steroid biosynthesis. These results suggest that trilostane is a safe, feasible therapeutic agent for long-term treatment of idiopathic hyperaldosteronism.
Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic Paradigm
AbstractNearly seven decades have elapsed since the clinical and biochemical features of primary hyperaldosteronism (PA) were described by Conn. PA is now widely recognized as the most common form of secondary hypertension. PA has a strong correlation with cardiovascular disease and failure to recognize and/or properly diagnose this condition has profound health consequences. With proper identification and management, PA has the potential to be surgically cured in a proportion of affected individuals. The diagnostic pursuit for PA is not a simplistic endeavor, particularly because an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm. These new concepts have emerged in all areas of this clinical condition, including identification, diagnosis, and treatment. Here, we review the recent advances in this field and summarize the effect these advances have on both diagnostic and therapeutic modalities.
AbstractBACKGROUND: Tumors known derived from kidneys which take place in secondary hyperaldosteronism etiology are juxtaglomerular cell tumor and Wilms' tumor. Neuroblastoma presenting with hyperaldosteronism is rare. CASE: A 15-month-old girl who had been having diarrhea and fever for 2 weeks presented with a 3 day history of bilious vomiting, metabolic acidosis and severe hypokalemia. She was referred to our hospital with the pre-diagnosis of unknown manifest hypertension etiology, diarrhea, and paralytic ileus after having therapy-resistant hypokalemia and severe resistant acidosis. On her examination after being admitted to our clinic, she was weak, unwell and lethargic with a blood pressure of 140/93 mmHg. Due to the hypertension and severe hypokalemia, the patient was considered to be hyperaldosteronism. Serum aldosterone level, plasma renin activity and cortisol level were elevated. Radiologic findings were compatible with neuroblastoma. The patient underwent an abdominal surgery and the mass excision. The histopathological examination was proved neuroblastoma. CONCLUSION: Hyperaldosteronism can be presented by unexpected atypical forms as in our patient.
Problems of Endocrinology · 2010 · 3 citations · open access
The treatment of primary hyperaldosteronism
AbstractThe present review deals with the treatment of main nosological forms of primary hyperaldosteronism, such as aldosteron-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Much attention is given to perioperative management of APA patients for whom surgical treatment is the method of choice. Idiopathic hyperaldosteronism characterized by bilateral macro- and micronodular changes dictates the necessity of medicamentous therapy, in the first place with antagonists of mineralocorticoid receptors (e.g. spironolactone). Pharmacological standards of drug therapy are described for patients with IHA and those with APA in whom surgical treatment is impracticable.
Advances in molecular genetics of primary aldosteronism
AbstractPrimary aldosteronism is the most common reason of secondary hypertension,which can be divided into hereditary and sporadic.Gene fusion of CYP11B1 and CYP11B2 is the pathogenesis of familial hyperaldosteronism type Ⅰ,different fusion positions have different clinical manifestations.7p22 is the suspicious mutate gene position of familial hyperaldosteronism type Ⅱ,to which G protein coupled estrogen receptor gene should be given more attention.KNCJ5 gene mutation have been found related with familial hyperaldosteronism type Ⅲ and sporadic primary aldosteronism,which is germ line mutation and system mutation respectively,but it is not the only pathogenic mechanism.In animal experiments,knockout the weak rectifier type potassium channel Taskl and Task3 gene in mice made more successful hyperaldosteronism model in recent years.
Key words:
Primary aldosteronism; Familial hyperaldosteronism; Molecular genetics; KCNJ5
Long-term Medical Management of Aldosterone-Producing Adenoma
AbstractThis case of Conn's syndrome demonstrates long-term (seven years) efficacy of triamterene-thiazide therapy in controlling both hypertension and hypokalemia. Studies done before the adrenal tumor was removed surgically showed that the tumor had increased in size and function since the first studies were done before triamterene-thiazide therapy. The resolution of hypertension after nine years of hyperaldosteronism suggests that surgery is effective even after chronic hyperaldosteronism has been present for some time.
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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