ArticleOpen biology2022
NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors.
Article in Open biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Metformin treatment impairs the adenine nucleotide translocator activity and energy metabolism in human clear cell renal carcinoma cells.Scientific reports · 2026Article
- Mitochondrial Proteins in Putative Neuron-Derived Plasma Exosomes Are Altered in Parkinson's Disease: An Exploratory Study.Molecular neurobiology · 2026Article
- Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms.Nature structural & molecular biology · 2026Article
- NDUFS3 promotes proliferation via glucose metabolism reprogramming inducing AMPK phosphorylating PRPS1 to increase the purine nucleotide synthesis in melanoma.Cell death and differentiation · 2025Article
- Induced mitochondrial deficit by NDUFS3 transient silencing reduces RAB7 expression and causes lysosomal dysfunction in pancreatic cancer cells.Cell communication and signaling : CCS · 2025Article
- Molecular mechanisms of MAZ targeting up-regulation of NDUFS3 expression to promote malignant progression in melanoma.Communications biology · 2024Article
- Targeting cancer and immune cell metabolism with the complex I inhibitors metformin and IACS-010759.Molecular oncology · 2024Review
- Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy.Cell reports. Medicine · 2024Article
- Oxidative phosphorylation is a metabolic vulnerability of endocrine therapy and palbociclib resistant metastatic breast cancers.Nature communications · 2023Article
- The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington's Disease and Other Human Pathologies.International journal of molecular sciences · 2022Review
- NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors.Open biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of respiratory complex I (CI) is becoming a promising anti-cancer strategy, encouraging the design and the use of inhibitors, whose mechanism of action, efficacy and specificity remain elusive. As CI is a central player of cellular bioenergetics, a finely tuned dosing of targeting drugs is required to avoid side effects. We compared the specificity and mode of action of CI inhibitors metformin, BAY 87-2243 and EVP 4593 using cancer cell models devoid of CI. Here we show that both BAY 87-2243 and EVP 4593 were selective, while the antiproliferative effects of metformin were considerably independent from CI inhibition. Molecular docking predictions indicated that the high efficiency of BAY 87-2243 and EVP 4593 may derive from the tight network of bonds in the quinone binding pocket, although in different sites. Most of the amino acids involved in such interactions are conserved across species and only rarely found mutated in human. Our data make a case for caution when referring to metformin as a CI-targeting compound, and highlight the need for dosage optimization and careful evaluation of molecular interactions between inhibitors and the holoenzyme.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.