DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for multiple endocrine neoplasia type 1 — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMultiple endocrine neoplasia type 1 maps to a 8-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 multiple endocrine neoplasia type 1 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
ATM serine/threonine kinase (ATM) — ATM 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8OXQ · 2.5 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2007 study at the University of São Paulo, 154 individuals underwent clinical and genetic screening for multiple endocrine neoplasia type 1. Fifty-two MEN1 cases were identified: 13 index cases, 28 clinically diagnosed relatives, and 11 genetically diagnosed relatives. The genetically diagnosed group had a mean age of 27.0 years at diagnosis, significantly lower than the index cases (39.5 years) and clinically diagnosed group (42.4 years). In the genetically diagnosed group, 81.8% had one or no MEN1-related tumour, 45.4% were asymptomatic, and no metastasis or death was observed. Screening also excluded 102 non-carriers and identified one case of MEN1 phenocopy.
A 2021 retrospective cohort study compared 39 genotype-negative patients with clinical MEN1 to 63 genotype-positive MEN1 index cases. Genotype-negative patients were older at last follow-up (65 vs 50 years) and significantly older at their first and second primary manifestation. Only one genotype-negative patient developed a third primary manifestation. No genotype-negative patient with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumour. Disease-specific survival was significantly better in genotype-negative patients. Among those who had parathyroidectomy, 47% of genotype-negative patients had single-gland disease versus 0% in genotype-positive index cases. For duodenopancreatic neuroendocrine tumours, 17% were multifocal in genotype-negative patients versus 68% in genotype-positive index cases. Genotype-negative patients also had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas.
A 2012 review noted that no clear genotype-phenotype correlation has been established for MEN1, despite increased understanding of the menin protein. The review discussed exceptional clinical presentations that might offer clues to a possible correlation. A 2010 article emphasised that MEN1 phenocopy is an important differential diagnosis, particularly when diagnosis relies on sensitive but non-specific criteria such as mild hyperparathyroidism, pituitary microadenoma, and hyperprolactinaemia, and recommended confirmatory genetic testing.
What remains missing is prospective data on whether genotype-negative patients with clinical MEN1 derive equal benefit from standard surveillance regimens as genotype-positive patients. The retrospective data suggest a different clinical course, but no randomised or controlled prospective trial has tested tailored surveillance or treatment strategies for this subgroup. Funding for such trials, as well as for studies that can establish a genotype-phenotype correlation, is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinics · 2007 · 88 citations · open access
THE IMPACT OF CLINICAL AND GENETIC SCREENINGS ON THE MANAGEMENT OF THE MULTIPLE ENDOCRINE NEOPLASIA TYPE 1
AbstractTo perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome. Realizar rastreamentos clínico e gênico para Neoplasia Endócrina Múltipla tipo 1 (NEM1) e analisar seu impacto no seguimento clínico desses pacientes no Hospital das Clínicas, SP. O diagnóstico clínico de NEM1 foi realizado de acordo com o Consenso sobre neoplasias endócrinas múltiplas. A análise genética para identificação de mutações foi realizada por sequenciamento automático de todas as regiões codificadoras e fronteiras exon/intron do gene MEN1. Os casos afetados foram sub-divididos em 3 grupos e analisados separadamente: casos-índices (grupo I), familiares diagnosticados clinicamente (grupo II) e genicamente (grupo III). Um total de 154 casos participou desse estudo, sendo 52 diagnosticados com NEM1: 13 do grupo I, 28 do grupo II e 11 do grupo III. A idade média ao diagnóstico no grupo III (27 anos) foi significativamente menor que a dos grupos I (39,5 anos; p = 0,03) e II (42,4 anos; p = 0,01). A maioria dos pacientes dos grupos I e II apresentou 2 ou 3 tumores, enquanto que 81,8% dos casos do grupo III apresentavam 1 ou nenhum tumor relacionado à NEM1. Além disto, 45,4% dos casos do grupo III eram assintomáticos, não sendo observados nenhuma metástase ou óbito. Os demais 102 familiares sob-risco estudados não herdaram mutação MEN1 e foram excluídos do rastreamento clínico. Um caso de fenocópia NEM1 foi também localizado. Nossos dados demonstraram importantes benefícios no seguimento dos pacientes NEM1, obtidos pela implementação dos rastreamentos clínico e gênico para essa doença.
Variable clinical expression in patients with a germline MEN1 disease gene mutation: clues to a genotype–phenotype correlation
AbstractMultiple endocrine neoplasia type 1 is an inherited endocrine tumor syndrome, predominantly characterized by tumors of the parathyroid glands, gastroenteropancreatic tumors, pituitary adenomas, adrenal adenomas, and neuroendocrine tumors of the thymus, lungs or stomach. Multiple endocrine neoplasia type 1 is caused by germline mutations of the multiple endocrine neoplasia type 1 tumor suppressor gene. The initial germline mutation, loss of the wild-type allele, and modifying genetic and possibly epigenetic and environmental events eventually result in multiple endocrine neoplasia type 1 tumors. Our understanding of the function of the multiple endocrine neoplasia type 1 gene product, menin, has increased significantly over the years. However, to date, no clear genotype-phenotype correlation has been established. In this review we discuss reports on exceptional clinical presentations of multiple endocrine neoplasia type 1, which may provide more insight into the pathogenesis of this disorder and offer clues for a possible genotype-phenotype correlation.
Clinical Endocrinology · 2010 · 0 citations · open access
Historia de la Iglesia en Chile, Vol. I. En los caminos de la conquista espiritual. [Reseña]
AbstractMultiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.
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.
