DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for noonan syndrome 12 — 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 moduleNoonan syndrome 12 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 noonan syndrome 12 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
RAS related 2 (RRAS2) — RRAS2 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…
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RCSB Protein Data Bank · entry 9B4S · 3.1 Å · ligand (2S)-2-({2-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl}oxy)propanamide (5H5). Experimental structure, not a prediction.
What the evidence adds up to
Noonan syndrome is an autosomal dominant multisystem disorder caused by dysregulation of the RAS/MAPK pathway. Estimated incidence ranges from 1 per 1,000 to 1 per 2,500 live births, though one review cites 1–2 per 20,000 newborns. Typical features include short stature, cardiovascular abnormalities, characteristic facies, learning difficulties, developmental delay, bleeding manifestations, and lymphatic malformation. Most individuals live a normal life. The condition affects both sexes.
In a 2015 cohort of 50 Brazilian probands who were negative for pathogenic variants in the 11 known Noonan syndrome genes, whole-exome sequencing identified rare missense variants in SOS2 in 4% and in LZTR1 in 8%. SOS2 and LZTR1 variants also segregated in one American and one Polish family. The authors concluded that mutations in these two genes account for approximately 3% of all Noonan syndrome cases. SOS2 is homologous to SOS1, and its variants were found in patients with marked ectodermal involvement. The functional role of LZTR1 in the RAS/MAPK pathway was not known at the time of that study.
Multiple genotype-phenotype analyses have identified mutations in PTPN11, SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, RIT1, SOS2, LZTR1, and A2ML1 that result in Noonan syndrome, typically involving hyperactivation of the RAS-MAPK pathway. A 2019 report described a novel RIT1 mutation associated with deterioration of cardiac hypertrophy. No drug treatment is mentioned in any of these abstracts. What remains missing is any clinical trial testing a repurposed drug for Noonan syndrome, any functional study linking LZTR1 to RAS/MAPK signalling in a way that suggests a druggable target, and any patient stratification that might identify which genetic subtypes respond to which interventions.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 2015 · 245 citations · open access
Rare variants in <i>SOS2</i> and <i>LZTR1</i> are associated with Noonan syndrome
AbstractBACKGROUND: Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. METHODS: A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. RESULTS: We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. CONCLUSIONS: We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome.
AbstractNoonan syndrome is a relatively common dysmorphic syndrome. The typical features include short stature, cardiovascular abnormalities and a characteristic facies. Children with Noonan syndrome have a considerable number of potential health problems, which are highlighted in this article. However, most individuals with this condition live a normal life.
Clinical and Genetic Characteristics of Noonan Syndrome and Noonan-like Diseases
AbstractNoonan syndrome (NS) is a group of inherited autosomal dominant diseases characterized by a disturbance of the RAS-MAPK signaling pathway and leading to various clinical manifestations. The prevalence in the world is estimated at 1–2 per 20 000 newborns. The review discusses the molecular genetic causes of the disease, the characteristics of the clinical manifestations of the disease, and the methods of molecular genetic diagnosis.
A novel RIT1 mutation causes deterioration of Noonan syndrome-associated cardiac hypertrophy
AbstractNoonan syndrome (NS) is an autosomal dominant inherited condition characterized by unusual facial features, short stature, congenital heart disease, bleeding problems, metabolic and endocrine abnormalities, and other problems [1]. An estimated 1 in 1000–2500 live births are affected by various forms of the disease [2]. Multiple genotype-phenotype analyses have revealed numerous gene mutations (PTPN11, SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, RIT1, SOS2, LZTR1, and A2ML1) that result in NS, typically involving hyperactivation of the RAS-MAPK pathway and leading to various developmental disorders.
Journal of Medical Science And clinical Research · 2019 · 1 citations · open access
Noonan Syndrome – A Case Report
AbstractNoonan syndrome is an autosomal dominant multisystem disorder, associated with cardiac anomalies and a distinctive facial appearance, characterized by genetic heterogeneity. Noonan syndrome affects both females and males, and has an estimated incidence of 1 per 1,000-2,500 live births. The present report aims at presenting the oro-facial findings in a case of Noonan syndrome in a 16 year-old male.
Journal of Evolution of Medical and Dental Sciences · 2015 · 0 citations · open access
NOONAN SYNDROME: AN EARLY DIAGNOSIS
AbstractNoonan syndrome is a genetic multisystem disorder characterised by facial dysmorphism, learning difficulties, developmental delay, short stature, cardiac defects, bleeding manifestations and lymphatic malformation affecting 1 in 1000-2500 children. This is a case report of a twenty six month old boy diagnosed to have Noonan syndrome with sporadic inheritance secondary to advanced paternal age. Multidisciplinary approach is the key to success in managing these children, who are diagnosed at an early age.
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.
