DeCure for Combined oxidative phosphorylation deficiency 40
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for combined oxidative phosphorylation deficiency 40 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCombined oxidative phosphorylation deficiency 40 maps to a 2-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 combined oxidative phosphorylation deficiency 40 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.
What the evidence adds up to
The first abstract is a general 1959 review of oxidative phosphorylation and contains no data on disease or patients. The second abstract studies 85 endometrial carcinoma patients, not combined oxidative phosphorylation deficiency 40. It reports that copy-number-high tumours reflect TP53 inactivation, that TP53-inactive tumours have poor prognosis regardless of TP53 mutation status, and that overexpression of aurora kinase A and activation of oxidative phosphorylation are found in those tumours. The authors suggest PI3K/mTOR and autophagy pathways as potential drug targets for that cancer subtype. No drug is tested, no survival or response rates are given, and the work is entirely in tumour tissue, not in patients with a mitochondrial disease.
The third abstract is a 2009 review of combined oxidative phosphorylation deficiencies. It states that mitochondrial disorders are among the most common inherited human diseases, are often multisystemic and early fatal, and are caused by defects in the five OXPHOS complexes. It notes that identifying the genetic defect underlying a combined OXPHOS deficiency is difficult because of the many proteins and processes involved in mitochondrial translation and OXPHOS biogenesis. The review does not name a specific disease number (combined oxidative phosphorylation deficiency 40 is not mentioned), does not report any patient outcomes, and does not test any drug.
No abstract provides any clinical trial, any treatment tested in patients with combined oxidative phosphorylation deficiency 40, or any survival or response data for that disease. What is missing is any dedicated clinical study of the condition, any patient cohort with a confirmed genetic diagnosis of combined oxidative phosphorylation deficiency 40, any drug repurposing screen in relevant cell or animal models, and any funding or trial design aimed at that specific deficiency.
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 Pharmacy and Pharmacology · 1959 · 12 citations
Oxidative Phosphorylation
AbstractJournal Article Oxidative Phosphorylation Get access J D Judah J D Judah Department of Morbid Anatomy, University College Hospital Medical School, London Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 11, Issue 1, September 1959, Pages 1–16, https://doi.org/10.1111/j.2042-7158.1959.tb12518.x Published: 12 April 2011
International Journal of Gynecological Cancer · 2021 · 9 citations · open access
Activation of oxidative phosphorylation in TP53-inactive endometrial carcinomas with a poor prognosis
Abstract<h3>Objective</h3> We aimed to identify pathways for potential therapeutic targets by conducting molecular profiling of endometrial carcinomas in patients with poor prognosis. <h3>Methods</h3> The classification of endometrial carcinomas has undergone a paradigm shift with the advent of next generation sequencing based molecular profiling. Although this emerging classification reflects poor prognosis in patients with endometrial carcinoma, knowledge of affected biological pathways is still lacking. In this study, 85 patients with endometrial carcinomas at the Shizuoka Cancer Center were evaluated from January 2014 to March 2019 and classified based on The Cancer Genome Atlas subgroups. The accumulation of germline and somatic mutations was determined using next generation sequencing. Gene expression profiling was used to determine the effect of TP53 inactivation on the recurrence of endometrial carcinoma. Additionally, the biological pathways associated with TP53 inactivation were estimated by pathway analysis based on gene expression. <h3>Results</h3> Based on The Cancer Genome Atlas classification, the ratio of polymerase-epsilon to copy number-high subgroups and the frequency of <i>PTEN</i> and <i>TP53</i> mutations differed in patients, and mutations of <i>ARHGAP35</i> observed in normal endometrium were accumulated in the polymerase-epsilon and microsatellite instability subgroups. We revealed that copy number-high reflects TP53 inactivation in endometrial carcinomas, and that TP53-inactive tumors with or without <i>TP53</i> mutations have poor prognosis. Furthermore, overexpression of aurora kinase A and activation of oxidative phosphorylation were found in TP53-inactivated endometrial carcinomas, suggesting that the PI3K/mTOR and autophagy pathways are potential drug targets. <h3>Conclusion</h3> Our analysis revealed a relationship between pathways involved in oxidative phosphorylation and poor prognosis and provides insight into potential drug targets.
Psychological Science and Education · 2009 · 0 citations
Self-Perception Peculiarities of Adolescents at Risk of Getting into Residential Care
AbstractMitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders.
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.
