DeCure.ai

Rare & Orphan Lab · DeCure for X

DeCure for Adrenocortical insufficiency

DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for adrenocortical insufficiency — 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 module4 genesLead labRare & Orphan
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Rare & OrphanDOID:10493$DeCureRare

The disease map

Disease moduleAdrenocortical insufficiency 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

Current lead

No approved-drug candidate for adrenocortical insufficiency 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

nuclear receptor subfamily 5 group A member 1 (NR5A1) — NR5A1 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 2sdrag to rotate · scroll to zoom

RCSB Protein Data Bank · entry 4QJR · 2.4 Å · ligand (2S)-3-{[(R)-{[(1S,2S,3R,4S,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxy}(hydroxy)phosphoryl]oxy}propane -1,2-diyl dihexadecanoate (PIZ). Experimental structure, not a prediction.

Evidence

Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.

New England Journal of Medicine · 1953 · 157 citations

Pharmacologic Aspects of Adrenocortical Steroids and ACTH in Man

AbstractTHE importance of the adrenocortical steroids as essential mediators of metabolic processes is well established. In the treatment of adrenocortical insufficiency these hormones are capable of restoring severely ill patients to a state of health that is remarkably near normal. In the wider field of inflammatory diseases their action is no less dramatic, although the indications for their use and their ultimate place in the therapeutic armamentarium are not yet clearly defined. Experience has emphasized the necessity for exercising unusual care in initiating or terminating a therapeutic trial with these agents. Regardless of the extent to which they may eventually . . .

https://doi.org/10.1056/nejm195302052480604
Annals of Internal Medicine · 1997 · 34 citations

The Changing Clinical Spectrum of Adrenal Insufficiency

AbstractEditorials15 December 1997The Changing Clinical Spectrum of Adrenal InsufficiencyRobert M. Carey, MDRobert M. Carey, MDUniversity of Virginia School of Medicine; Charlottesville, VA 22908.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-12-199712150-00009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The clinical spectrum of primary adrenal insufficiency has changed substantially over the past decade as a result of the emergence of new disease patterns, improved understanding of clinical presentations, and the impact of molecular genetics. I comment here on five clinical entities that have emerged as new diagnostic or therapeutic challenges in the 1990s.Adrenal insufficiency is increasingly recognized in patients with AIDS [1-3], and it correlates with stage of progression of HIV infection. More than 50% of patients with AIDS have pathologic evidence of necrotizing adrenalitis, but the degree of adrenal destruction is usually less than 50%. Clinical adrenal ...References1. Piedrola G, Casado JL, Lopez E, Moreno A, Perez-Elias MJ, Garcia-Robles R. Clinical features of adrenal insufficiency in patients with acquired immunodeficiency syndrome. Clin Endocrinol (Oxf). 1996; 45:97-101. Google Scholar2. Freda PU, Wardlaw SL, Brudney K, Goland RS. Primary adrenal insufficiency in patients with the acquired immunodeficiency syndrome: a report of five cases. J Clin Endocrinol Metab. 1994; 79:1540-5. Google Scholar3. Amason JA, Graziano FM. Adrenal insufficiency in the antiphospholipid antibody syndrome. Semin Arthritis Rheum. 1995; 25:109-16. Google Scholar4. Bevilacqua M. Hyponatremia in AIDS. Baillieres Clin Endocrinol Metab. 1994; 8:837-48. Google Scholar5. May ME, Vaughan ED Jr, Carey RM. Adrenocortical insufficiency-clinical aspects. In: Vaughan ED Jr, Carey RM, eds. Adrenal Disorders. New York: Thieme Medical; 1989:171-89. Google Scholar6. Burke CW. Adrenocortical insufficiency. Clin Endocrinol Metab. 1985; 14:947-76. Google Scholar7. Chin R. Adrenal crisis. Crit Care Clin. 1991; 7:23-42. Google Scholar8. Siu SC, Kitzman DW, Sheedy PF 2d, Northcutt RC. Adrenal insufficiency from bilateral adrenal hemorrhage. Mayo Clin Proc. 1990; 65:664-70. Google Scholar9. Winqvist O, Gustafsson J, Rorsman F, Karlsson FA, Kampe O. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison's disease. J Clin Invest. 1993; 92:2377-85. Google Scholar10. Uibo R, Aavik E, Peterson P, Perheentupa J, Aranko S, Pelkonen R, et al. Autoantibodies to cytochrome P450 enzymes P450scc, P450c17, and P450c21 in autoimmune polyglandular disease types I and II and in isolated Addison's disease. J Clin Endocrinol Metab. 1994; 78:323-8. Google Scholar11. Winqvist O, Gebre-Medhin G, Gustafsson J, Ritzen EM, Lundkvist O, Karlsson FA, et al. Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure. J Clin Endocrinol Metab. 1995; 80:1717-23. Google Scholar12. Chen S, Sawicka J, Betterle C, Powell M, Prentice L, Volpato M, et al. Autoantibodies to steroidogenic enzymes in autoimmune polyglandular syndrome, Addison's disease, and premature ovarian failure. J Clin Endocrinol Metab. 1996; 8:1871-6. Google Scholar13. Furmaniak J, Kominami S, Asawa T, Wedlock N, Colls J, Smith BR. Autoimmune Addison's disease-evidence for a role of steroid 21-hydroxylase autoantibodies in adrenal insufficiency. J Clin Endocrinol Metab. 1994; 79:1517-21. Google Scholar14. Boscaro M, Betterle C, Sonino N, Volpato M, Paoletta A, Fallo F. Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency. J Clin Endocrinol Metab. 1994; 79:452-5. Google Scholar15. De Bellis A, Bizzarro A, Rossi R, Paglionico VA, Criscuolo T, Lombardi G, et al. Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies. J Clin Endocrinol Metab. 1993; 76:1002-7. Google Scholar16. Moser HW. Adrenoleukodystrophy. Curr Opin Neurol. 1995; 8:221-6. Google Scholar17. Aubourg P. Adrenoleukodystrophy and other peroxisomal diseases. Curr Opin Genet Dev. 1994; 4:407-11. Google Scholar18. Wanders RJ, Schutgens RB, Barth PG. Peroxisomal disorders: a review. J Neuropathol Exp Neurol. 1995; 54:726-39. Google Scholar19. Blevins LS Jr, Shankroff J, Moser HW, Ladenson PW. Elevated plasma adrenocorticotropin concentration as evidence of limited adrenocortical reserve in patients with adrenomyeloneuropathy. J Clin Endocrinol Metab. 1994; 78:261-5. Google Scholar20. Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison's disease in young adult male patients. J Clin Endocrinol Metab. 1996; 81:470-4. Google Scholar21. Tsigos C, Arai K, Latronico AC, DiGeorge AM, Rapaport R, Chrousos GP. A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome. J Clin Endocrinol Metab. 1995; 80:2186-9. Google Scholar22. Weber A, Clark AJ. Mutations of the ACTH receptor gene are only one cause of familial glucocorticoid deficiency. Hum Mol Genet. 1994; 3:585-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Virginia School of Medicine; Charlottesville, VA 22908.Corresponding Author: Robert M. Carey, MD, Box 395, University of Virginia Health Sciences Center, Charlottesville, VA 22908. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNeuromuscular Manifestations of Acquired Metabolic, Endocrine, and Nutritional DisordersSteroid Therapy in Adrenal InsufficiencyClinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassayThe Adrenal CortexNeurologic complications of disorders of the adrenal glandsNeurologic complications of multiple endocrine syndromesCardiovascular Manifestations of Endocrine DysfunctionThe Adrenal CortexNeuromuscular Manifestations of Acquired Metabolic, Endocrine, and Nutritional DisordersAddison's Disease From Non-Hodgkin's Lymphoma With Normal-Size Adrenal GlandsCT diagnosis of acute adrenal insufficiency due to bilateral adrenal haemorrhageNeurohormonal FactorsRecognition and Management of Adrenal EmergenciesAdrenal hemorrhage mimicking an acute abdomenAntiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis?Autoantibodies in autoimmune polyendocrine syndrome type IIAdrenal Insufficiency in Critically Ill PatientsPrimary hypoadrenalism assessed by the 1 μg ACTH test in hospitalized patients with active pulmonary tuberculosis 15 December 1997Volume 127, Issue 12Page: 1103-1105KeywordsAIDSAdrenocorticotropic hormoneAutoantibodiesCholesterolEnzymesFatty acidsHemorrhageSteroidogenesisThrombosisType 1 diabetes Issue Published: 15 December 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. 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https://doi.org/10.7326/0003-4819-127-12-199712150-00009

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.