DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for sleep-wake disorder — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSleep-wake disorder maps to a 3-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
Structures already discussed alongside sleep-wake disorder in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
PanDDA analysis group deposition -- Crystal Structure of DCLRE1A — Agomelatine has a real, experimentally solved structure in complex with this target (PDB 5Q1S, 1.62 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet awydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5Q1S · 1.62 Å · ligand Agomelatine (AWY). Experimental structure, not a prediction.
What the evidence adds up to
Medication is indicated for only a limited number of children's sleep disorders. Where medication is appropriate, cautious use and careful review of the child's physical and psychological state is essential because there is limited information available on effectiveness and possible short and long term effects. Much further research is required to establish the part medication can play in the care of children with sleep disorders, and also to define the possible effects on sleep and wakefulness of other drugs used in clinical practice.
The range of drugs used for the treatment of sleep disorders is quite extensive, and not all of them are true sleeping pills. Such pills often belong to various classes of psychotropic medications. Domestic and foreign studies and guidelines from the Russian Society of Somanologists (2016), the European Sleep Research Society (2017), the American Academy of Sleep Medicine (2017), and the American College of Physicians (2016) show that normalisation of sleep in patients with insomnia by various methods, including pharmacotherapy, neutralises its negative effects, improves adaptive capacity, and prevents chronic sleep disorders with severe adverse effects.
Only four rare sleep disorders have an established genetic basis that may result from a single gene mutation: fatal familial insomnia, familial advanced sleep-phase syndrome, chronic primary insomnia, and narcolepsy with cataplexy. Most sleep disorders are complex in terms of genetic susceptibility together with variable expressivity of the phenotype even within a same family. Recent linkage, genome-wide and candidate gene association studies have identified gene mutations, gene localisations, or evidence for susceptibility genes in several sleep disorders. Molecular techniques including genome-wide linkage and association studies are further required to identify the contribution of new genes.
Clinical trials in sleep medicine cover a wide range of sleep–wake problems, and the selection of outcome measures needs to be tailored to the specific disorder under examination. The review describes measures most commonly used in sleep medicine clinical trials, weighing the relative merits of a self-report questionnaire versus a physiologic test as the a priori primary outcome measures. What is still missing is systematic paediatric pharmacokinetic and safety data for most hypnotic drugs, validated genetic biomarkers that could stratify patients for targeted treatment, and clinical trial designs that move beyond subjective sleep diaries to objective, disorder-specific endpoints.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Disease in Childhood · 2003 · 41 citations · open access
Medication for sleep-wake disorders
AbstractMedication is indicated for only a limited number of children's sleep disorders. However, correctly chosen and supervised, pharmacological treatment may be justified and helpful. For a given sleep problem it is important to identify the underlying cause (or sleep disorder) which often calls for treatment of a non-medication type. Where medication is appropriate, cautious use and careful review of the child's physical and psychological state is essential in view of the limited information available on effectiveness and possible short and long term effects. It follows that much further research is required to establish the part medication can play in the care of children with sleep disorders, and also to define the possible effects on sleep and wakefulness of other drugs used in clinical practice.
Current Pharmaceutical Design · 2008 · 26 citations
The Genetic Basis of Sleep Disorders
AbstractThe contribution of genes, environment and gene-environment interactions to sleep disorders is increasingly recognized. Well-documented familial and twin sleep disorder studies suggest an important influence of genetic factors. However, only few sleep disorders have an established genetic basis including four rare diseases that may result from a single gene mutation: fatal familial insomnia, familial advanced sleep-phase syndrome, chronic primary insomnia, and narcolepsy with cataplexy. However, most sleep disorders are complex in terms of their genetic susceptibility together with the variable expressivity of the phenotype even within a same family. Recent linkage, genome-wide and candidate gene association studies resulted in the identification of gene mutations, gene localizations, or evidence for susceptibility genes and/or loci in several sleep disorders. Molecular techniques including mainly genome-wide linkage and association studies are further required to identify the contribution of new genes. These identified susceptibility genetic determinants will provide clues to better understand pathogenesis of sleep disorders, to assess the risk for diseases and also to find new drug targets to treat and to prevent the underlying conditions. We reviewed here the role of genetic basis in most of key sleep disorders.
Meditsinskiy sovet = Medical Council · 2018 · 9 citations · open access
Pharmacotherapy treatment principles for insomnia
AbstractPharmacotherapy of insomnia is an integral part of the treatment of this clinical syndrome. The range of drugs used for the treatment of sleep disorders is quite extensive, and not all of them are “true” sleeping pills”. Such pills often belong to the various classes of psychotropic medications. Advanced sleeping pills taken in compliance with the necessary rules provide the necessary sleeping effect without accompanied negative changes in the sleep structure and the quality of the subsequent waking. The domestic and foreign studies, the leading professional community guidelines (the Russian Society of Somanologists – 2016, the European Sleep Research Society – 2017, the American Academy of Sleep Medicine – 2017, the American College of Physicians – 2016) show that normalization of sleep in patients with insomnia by various methods, including pharmacotherapy, neutralizes its negative effects, improves the adaptive capacity of the individual and prevents the chronic sleep disorders with severe adverse effects.
International Journal of Psychiatry in Clinical Practice · 2014 · 8 citations
Subgroup analysis of the non-interventional study VIVALDI: Agomelatine in treatment-naïve patients, in combination therapy and after treatment switch
AbstractOBJECTIVE: Agomelatine has demonstrated antidepressant efficacy in randomized, controlled trials. This non-interventional study VIVALDI evaluated agomelatine treatment under practice conditions. METHODS: Psychiatrists documented the treatment of 3,317 patients over 12 weeks. According to the treatment condition three subgroups were selected: Agomelatine in treatment-naïve patients as mono-therapy (A), in pretreated patients as add-on-therapy (B), and in pretreated patients switched to agomelatine (C). Effect on depressive symptoms was evaluated via svMADRS and CGI. Daytime functioning and sleep-wake rhythm were assessed by a patient-questionnaire. RESULTS: The svMADRS decreased from values > 30 at baseline to 12.8 (total population), 10.3 (A), 15.1 (B), and 13.5 (C). 76.1%, 55.7%, and 62.5% of patients were responders in subgroups A, B, and C, respectively, 65.8% in the total population. Remission was achieved in 66.5% (A), 44.7% (B), and 50.9% (C) of patients. After 12 weeks, subjective sleep quality and daytime functioning improved in the majority of patients. Adverse drug reactions (ADR/serious ADR) were reported for 6.0%/0% (A), 11.0%/0.2% (B), and 12.6%/0.3% (C) of patients. Overall, 25.8% of patients discontinued treatment prematurely, 5.2% due to ADR. CONCLUSION: Agomelatine improved depressive symptoms, daytime functioning, and sleep-wake rhythm, and demonstrated good tolerability also in pretreated patients and combination therapy under routine practice.
Assessment methodologies in sleep medicine clinical trials
AbstractClinical trials in sleep medicine cover a wide range of sleep–wake problems, and accordingly the selection of outcome measures in sleep medicine clinical trials needs to be tailored to the specific disorder under examination. This review describes the measures most commonly used in sleep medicine clinical trials, weighing the relative merits of a self-report questionnaire versus a physiologic test as the a priori primary outcome measures.
AbstractSleep disorders are among the most common clinical ailments, and molecular research is beginning to shed light on the neurobio-logy of sleep and the mechanisms underlying specific disorders of sleep. This chapter focuses on sleep disorders with a neurological basis, particularly those in which recent discoveries have realed the underlying molecular biology.
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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