DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Carney-Stratakis syndrome — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCarney-Stratakis syndrome maps to a 7-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 carney-stratakis syndrome 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
von Hippel-Lindau tumor suppressor (VHL) — VHL 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 2s,4rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8QVU · 2.24 Å · ligand (2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]butoxy]-1,2,3-triazol-1-yl]-3-methyl-butanoyl]-N-[(1R)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-2-oxidanyl-ethyl]-4-oxidanyl-pyrrolidine-2-carboxamide (WYL). Experimental structure, not a prediction.
What the evidence adds up to
Carney-Stratakis syndrome is defined by the combination of a paraganglioma and a gastrointestinal stromal tumour, distinct from the Carney Triad which also includes a pulmonary chondroma. The syndrome has autosomal dominant inheritance with incomplete penetrance. Germline mutations of succinate dehydrogenase (SDH) complex subunits, and consequent SDH functional deficiency, have been identified as responsible for the condition. A 2023 case report describes a new mutation site in SDHB that had not previously been reported.
Carney complex, a separate dominantly inherited syndrome, involves endocrine tumours (thyroid, pituitary, adrenocortical, gonadal), non-endocrine tumours (myxomas, pigmented skin lesions), and neural tumours (schwannomas). Primary pigmented nodular adrenocortical disease (PPNAD) is its most common endocrine manifestation and the only inherited form of Cushing syndrome known as of 2003. Heterozygous inactivating mutations of PRKAR1A, encoding the type I-alpha regulatory subunit of protein kinase A, were reported in about 45% of Carney complex index cases and in about 80% of families presenting mainly with Cushing syndrome. Somatic mutations of PRKAR1A have been found in PPNAD and in a subset of sporadic secreting adrenocortical adenomas with features similar to PPNAD.
The abstracts provide no data on any drug treatment, response rates, survival, or clinical outcomes for Carney-Stratakis syndrome. No drug is mentioned in any of the abstracts. The literature reviewed is entirely descriptive of genetics and syndrome definition.
What is missing: any clinical trial testing a drug in Carney-Stratakis syndrome, any data on whether SDH deficiency can be targeted pharmacologically, and any patient stratification beyond mutation identification. Money for preclinical models and for a trial large enough to detect benefit in this rare syndrome has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
FEBS Letters · 2003 · 86 citations
Human tumors associated with Carney complex and germline <i>PRKAR1A</i> mutations: a protein kinase A disease!
AbstractCarney complex (CNC) is a multiple neoplasia syndrome that consists of endocrine (thyroid, pituitary, adrenocortical and gonadal), non-endocrine (myxomas, nevi and other cutaneous pigmented lesions), and neural (schwannomas) tumors. Primary pigmented nodular adrenocortical disease (PPNAD) is the most common endocrine manifestation of CNC and the only inherited form of Cushing syndrome known to date. In the search of genes responsible for CNC, two chromosomal loci were identified; one (17q22-24) harbored the gene encoding the type I-alpha regulatory subunit (RIalpha) of protein kinase A (PKA), PRKAR1A, a critical component of the cAMP signaling pathway. Here we review CNC and the implications of this discovery for the cAMP and/or PKA's involvement in human tumorigenesis.
Hormone Research in Paediatrics · 2005 · 39 citations
Adrenal Pathophysiology: Lessons from the Carney Complex
AbstractThe Carney complex (CNC) is a dominantly inherited syndrome responsible mainly for spotty skin pigmentation (lentiginosis), endocrine overactivity, and cardiac myxomas. Adrenocorticotropic hormone independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is a main characteristic of CNC. PPNAD is a very rare cause of Cushing's syndrome due to a primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations nor familial history. One of the putative CNC genes, located on 17q22-24, has been identified as the regulatory subunit R1A of protein kinase A (PRKAR1A). Heterozygous inactivating mutations of PRKAR1A have been reported initially in about 45% of the CNC index cases and could be found in about 80% of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cyclic AMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Interestingly, patients with isolated PPNAD and no familial history of CNC can also present a germline de novo mutation of PRKAR1A. Somatic mutations of PRKAR1A have been found in PPNAD as a mechanism of inactivation of the wild-type allele, in a patient already presenting a germline mutation, and in a subset of sporadic secreting adrenocortical adenomas with clinical, hormonal, and pathological features quite similar to PPNAD. This review will summarize the recent findings on CNC from the perspective of the pathophysiology of adrenal Cushing's syndrome and PPNAD.
Fetal and Pediatric Pathology · 2000 · 11 citations
Genetics of Carney Complex and Related Familial Lentiginoses, and other Multiple Tumor Syndromes
AbstractCarney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the. gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.
Fetal and Pediatric Pathology · 2000 · 8 citations
GENETICS OF CARNEY COMPLEX AND RELATED FAMILIAL LENTIGINOSES, AND OTHER MULTIPLE TUMOR SYNDROMES
AbstractCarney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the. gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.
Radiology Case Reports · 2020 · 2 citations · open access
Carney-Stratakis Syndrome presenting as occult mediastinal paraganglioma
AbstractCarney-Stratakis Syndrome is defined as the combination of a paraganglioma and a gastrointestinal stromal tumor. This is recognized as unique from the more commonly known Carney Triad, which in addition to the above also has a pulmonary chondroma present. We present a case of Carney-Stratakis Syndrome which highlights the value of multimodality imaging in arriving at the diagnosis, as well as the role of genetic testing for definitively differentiating it from the more commonly recognized Carney Triad.
Journal of Disease Markers · 2023 · 0 citations · open access
A New Mutation Site of Succinate Dehydrogenase-Related Carney-Stratakis Syndrome: A Case Report
AbstractCarney-Stratakis Syndrome (CSS), first described in 2002 [1], encompasses Gastrointestinal Stromal Tumors (GISTs) and Paragangliomas (PGLs) and has autosomal dominant inheritance with incomplete penetrance [2]. Germline mutations of Succinate Dehydrogenase (SDH) complex subunits and consequent SDH functional deficiency have been identified as responsible for CSS [3]. Here, we present a case with a new mutation site in SDHB that has not yet been reported.
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.
