DeCure for Combined oxidative phosphorylation deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for combined oxidative phosphorylation deficiency — screening already-approved drugs against its 12-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 maps to a 12-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 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
latexin (LXN) — LXN 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 valdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2BO9 · 1.6 Å · ligand VALINE (VAL). Experimental structure, not a prediction.
What the evidence adds up to
The 2010 review of combined oxidative phosphorylation deficiencies describes them as a heterogeneous group of often multisystemic and early fatal diseases, among the most common inherited human diseases. These disorders are caused by defects in the OXPHOS system, which comprises five multisubunit enzyme complexes encoded by both nuclear and mitochondrial genomes. The review notes that identifying the genetic defect underlying a combined OXPHOS deficiency is not an easy task, due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system. The authors state that knowledge of the proteins and processes involved in mitochondrial translation and OXPHOS biogenesis is important for further research into genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders.
A 2022 review on targeting OXPHOS in cancer states that OXPHOS takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. The review notes that it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. The review describes current therapeutic approaches and challenges in targeting OXPHOS and the electron transport chain for cancer therapy, but provides no clinical data on any specific drug or outcome in patients.
A 1951 paper describes that low concentrations of 2:4-dinitrophenol (DNP) reversibly uncouple the phosphorylation associated with the oxidation of glutamate. The paper states that DNP prevents the use of energy provided by respiration and glycolysis by inhibiting the formation of high-energy phosphate bonds, and that it accelerates respiration and glycolysis of intact cells. A 1959 paper on oxidative phosphorylation provides no clinical data on any disease or treatment.
No abstract reports any clinical trial, survival data, response rates, or patient outcomes for any drug in combined oxidative phosphorylation deficiency. What is missing is any clinical trial testing a specific intervention in patients with this disease, any validated biomarker for patient stratification, and the funding to move from basic mechanistic description to a therapeutic candidate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Cancer Biology · 2022 · 213 citations · open access
Targeting OXPHOS and the electron transport chain in cancer; Molecular and therapeutic implications
AbstractOxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges.
BioMed Research International · 2010 · 198 citations · open access
Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies
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.
Biochemical Journal · 1951 · 120 citations · open access
The inhibition of oxidative phosphorylation
AbstractLoomis & Lipmann (1948) showed that low concen- trations of 2:4-dinitrophenol (DNP) reversibly un- couple the phosphorylation associated with the oxidation of glutamate. This supported the hypo- thesis that agents such as DNP, which prevent the use of the energy provided by respiration and glycolysis, do so by inhibiting the formation of high- energy phosphate bonds (Lardy & Elvehjem, 1945; McElroy, 1947). The acceleration of respiration and glycolysis of intact cells by low concentrations of DNP (see Meyerhof & Geliazkowa, 1947). Johnson (1941) has suggested that the Pasteur effect is a consequence of the greater efficiency of aerobic phosphorylation compared with that associated with glycolysis, a view which is consistent with the inhibition of the Pasteur effect by DNP (Dodds & Greville, 1934). Lynen (1941) has indeed shown that respiration reduces the amount of orthophosphate available for yeast fermentation.
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
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.
