ArticleNature chemical biology2014
Pharmacological targeting of the pseudokinase Her3.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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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.
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Who cites it
85 citing papers in PubMed, 197 citations in OpenAlex.
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Tissue-specific inflammation induces cell state plasticity with oncogenic addiction in mucosal melanoma.Science advances · 2026Article
- Hydrophobic tagging: A promising paradigm for targeted protein degradation.Cell insight · 2026Review
- Indirect ubiquitination independent of endogenous ubiquitination machinery for targeted protein degradation.Communications chemistry · 2026Article
- Proteolysis-targeting chimeras in cancer therapy: Targeted protein degradation for next-generation treatment.Cancer · 2025Review
- ERBB3 influences the ferroptosis pathway via modulation of lipid peroxidation and GSH synthesis in gastric cancer.Cell death discovery · 2025Article
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- Development of a novel anti-erythropoietin-producing hepatocellular receptor B6 monoclonal antibody EbBiochemistry and biophysics reports · 2025Article
- Discovery of the first selective and potent PROTAC degrader for the pseudokinase TRIB2.European journal of medicinal chemistry · 2025Article
- Article
- DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.EMBO molecular medicine · 2024Article
- Recent insights into the therapeutic strategies targeting the pseudokinase PTK7 in cancer.Oncogene · 2024Review
- Review
- Review
- Targeted protein degradation in cancers: Orthodox PROTACs and beyond.Innovation (Cambridge (Mass.)) · 2023Review
- Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence.Journal of the American Chemical Society · 2023Review
- Emerging TACnology: Heterobifunctional Small Molecule Inducers of Targeted Posttranslational Protein Modifications.Molecules (Basel, Switzerland) · 2023Review
- Review
25 more citing papers are in PubMed but not listed here.
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 6 institutions in 2 countries.
Funding
Abstract
Her3 (also known as ErbB3) belongs to the epidermal growth factor receptor tyrosine kinases and is well credentialed as an anti-cancer target but is thought to be 'undruggable' using ATP-competitive small molecules because it lacks appreciable kinase activity. Here we report what is to our knowledge the first selective Her3 ligand, TX1-85-1, that forms a covalent bond with Cys721 located in the ATP-binding site of Her3. We demonstrate that covalent modification of Her3 inhibits Her3 signaling but not proliferation in some Her3-dependent cancer cell lines. Subsequent derivatization with a hydrophobic adamantane moiety demonstrates that the resultant bivalent ligand (TX2-121-1) enhances inhibition of Her3-dependent signaling. Treatment of cells with TX2-121-1 results in partial degradation of Her3 and serendipitously interferes with productive heterodimerization between Her3 with either Her2 or c-Met. These results suggest that small molecules will be capable of perturbing the biological function of Her3 and ∼60 other pseudokinases found in human cells.
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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.