ArticleNature chemical biology2018
Facile target validation in an animal model with intracellularly expressed monobodies.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.Molecular cell · 2026Article
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.bioRxiv : the preprint server for biology · 2026Article
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- Improving the pharmacokinetics, biodistribution and plasma stability of monobodies.Frontiers in pharmacology · 2024Article
- Article
- Adaptable, turn-on maturation (ATOM) fluorescent biosensors for multiplexed detection in cells.Nature methods · 2023Article
- A generalizable nanopore sensor for highly specific protein detection at single-molecule precision.Nature communications · 2023Article
- Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Protein scaffolds: antibody alternatives for cancer diagnosis and therapy.RSC chemical biology · 2022Review
- Convergent Alterations of a Protein Hub Produce Divergent Effects within a Binding Site.ACS chemical biology · 2022Article
- Monobodies as tool biologics for accelerating target validation and druggable site discovery.RSC medicinal chemistry · 2021Review
- Kinetics of the multitasking high-affinity Win binding site of WDR5 in restricted and unrestricted conditions.The Biochemical journal · 2021Article
- Selective and noncovalent targeting of RAS mutants for inhibition and degradation.Nature communications · 2021Article
- A cell-based screening method using an intracellular antibody for discovering small molecules targeting the translocation protein LMO2.Science advances · 2021Article
- Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold.Nature communications · 2020Article
- Review
- Monobodies as enabling tools for structural and mechanistic biology.Current opinion in structural biology · 2020Review
- WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells.Breast cancer research : BCR · 2019Article
- Cytosolic delivery of inhibitory antibodies with cationic lipids.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Advances in targeted degradation of endogenous proteins.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Rapidly determining the biological effect of perturbing a site within a potential drug target could guide drug discovery efforts, but it remains challenging. Here, we describe a facile target validation approach that exploits monobodies, small synthetic binding proteins that can be fully functionally expressed in cells. We developed a potent and selective monobody to WDR5, a core component of the mixed lineage leukemia (MLL) methyltransferase complex. The monobody bound to the MLL interaction site of WDR5, the same binding site for small-molecule inhibitors whose efficacy has been demonstrated in cells but not in animals. As a genetically encoded reagent, the monobody inhibited proliferation of an MLL-AF9 cell line in vitro, suppressed its leukemogenesis and conferred a survival benefit in an in vivo mouse leukemia model. The capacity of this approach to readily bridge biochemical, structural, cellular characterization and tests in animal models may accelerate discovery and validation of druggable sites.
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What OpenQuestion 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 OpenQuestion graph.