DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for apparent mineralocorticoid excess — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleApparent mineralocorticoid excess maps to a 1-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 apparent mineralocorticoid excess 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.
What the evidence adds up to
Apparent mineralocorticoid excess is an extraordinarily rare autosomal recessive disorder, with less than 100 cases reported to date. It is caused by dysfunction of the 11-beta-hydroxysteroid type 2 enzyme due to pathogenic variants in HSD11B2. A 2025 report describes a novel homozygous pathogenic variant in this gene as the cause. The disorder is characterised by severe hypertension and hydroelectrolytic disorders. Initial suspicion and diagnosis are described as crucial for targeted treatment, improving prognosis and minimising complications.
One 1992 case report describes a patient with biological markers of hypermineralocorticoidism — hypokalaemia, low plasma and urinary aldosterone levels, and suppressed plasma renin activity — that was secondary to prolonged administration of a mineralocorticoid-containing nasal spray. This represents a factitious, rather than genetic, form of apparent mineralocorticoid excess.
A 1974 study in spontaneously hypertensive rats (SHR) examined whether a mineralocorticoid receptor abnormality could explain hypertension in that model. Binding assays with kidney slices from adrenalectomised rats found no significant difference between SHR and normal rats in the dissociation constant (Kdiss 25°C: 7 × 10⁻¹⁰ M for normal, 9 × 10⁻¹⁰ M for SHR) or maximum binding capacity (1.8 × 10⁻¹⁴ moles/mg protein for both). 18-hydroxydeoxycorticosterone was 1/50th as potent as aldosterone in binding to mineralocorticoid receptors in both strains. Cytoplasmic binding kinetics and nuclear uptake of ³H-aldosterone were comparable. The authors concluded that the underlying abnormality in SHR is not an alteration in steroid binding to renal mineralocorticoid receptors.
What is still missing is any controlled trial of a drug for the genetic form of apparent mineralocorticoid excess, given the extreme rarity of the condition. No patient stratification strategy has been prospectively tested, and no funding source has committed to a multi-centre registry or interventional study.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Endocrinology · 1974 · 6 citations
Mineralocorticoid Receptors and 18-Hydroxydeoxycorticosterone Binding in the Kidney of the Spontaneously Hypertensive Rat
AbstractMineralocorticoid excess in the form of elevated 18-hydroxydeoxycorticosterone (18-OH-DOC) has recently been implicated in some forms of genetic hypertension. Spontaneously hypertensiverats (SHR) of the Kyoto Wistar strain do not appear to secrete increased levels of this steroid compared to controls. If mineralocorticoids are etiologically involved, a plausible alternate hypothesis is that the genetic defect in these rats is an abnormality in the mineralocorticoid receptors present in target tissue. To evaluate this possibility, the renal mineralocorticoidreceptors of SHR were compared to those of normal rats (NR). Binding assays were performed with kidney slices from adrenalectomized rats utilizing 3Haldosterone and 10-fold excessunlabeled dexamethasone to prevent tracer binding to glucocorticoid sites. Scatchard analysis of 3H-aldosterone binding to the mineralocorticoid receptors revealed — NR: Kdiss(25C) = 7 × 10–10–10M and Nmnx= 1.8 × 10–14 moles/mg protein; SHR: Kdlss(25C) =9 × 10–10M and Nmnx= 1.8 X10–14 moles/mg protein. From competitive binding assays it was adduced that18-OH-DOC was 1/50th as potent as aldosterone in binding to the mineralocorticoid receptors in both NR and SHR. The kinetics of cytoplasmic binding and the extent of nuclear uptakeof 3H-aldosterone was comparable in the two strains. Thus, by the parameters studied,no significant difference existed in the mineralocorticoid receptors of NR and SHR. It is concluded that the underlying abnormality in SHR is not an alteration in steroid binding to renal mineralocorticoid receptors.(Endocrinology94: 1185, 1974)
Novel homozygous pathogenic variant in HSD11B2 as a cause of apparent mineralocorticoid excess
AbstractApparent mineralocorticoid excess is an extraordinarily rare autosomal recessive disorder, with less than 100 cases reported to date. This monogenic disorder, due to dysfunction of the 11-beta-hydroxysteroid type 2 enzyme, is characterized by severe hypertension and hydroelectrolytic disorders. The initial suspicion and diagnosis of this disease are crucial for targeted treatment, thereby improving the prognosis of these patients and minimizing complications.
An Unusual Cause of Factitious Mineralocorticoid Excess
AbstractThe presence of hypokalaemia in hypertensive patient must prompt a search for increased mineralocorticoid activity. We describe and discuss the observation of a patient with biological markers of hypermineralocorticoidism, despite low plasma and urinary aldosterone levels, and suppressed plasma renin activity. This typical syndrome of apparent mineralocorticoid excess was secondary, in our patient, to prolonged administration of a mineralocorticoid-containing nasal spray.
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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