ArticleNature chemical biology2017
Polypharmacology-based ceritinib repurposing using integrated functional proteomics.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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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
45 citing papers in PubMed, 97 citations in OpenAlex.
- Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial.The oncologist · 2023Trial
- A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- A Patient-Derived Organoid Biobank of Adamantinomatous Craniopharyngioma as a Platform for Drug Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanistic models position ceritinib as a nuclear integrity disrupting therapy in pediatric liver tumors.Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- Patient-derived organoids inform pharmacogenomic vulnerabilities in liver cancer.JHEP reports : innovation in hepatology · 2025Article
- Article
- De novo generation of multi-target compounds using deep generative chemistry.Nature communications · 2024Article
- Differential network analysis of ROS1 inhibitors reveals lorlatinib polypharmacology through co-targeting PYK2.Cell chemical biology · 2024Article
- Therapeutic Implications of Ceritinib in Cholangiocarcinoma beyond ALK Expression and Mutation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Exploring the role of Yuxuebi tablet in neuropathic pain with the method of similarity research of drug pharmacological effects based on unsupervised machine learning.Frontiers in pharmacology · 2024Article
- Catalytic Degraders Effectively Address Kinase Site Mutations in EML4-ALK Oncogenic Fusions.Journal of medicinal chemistry · 2023Article
- PROTEOMAS: a workflow enabling harmonized proteomic meta-analysis and proteomic signature mapping.Journal of cheminformatics · 2023Article
- A preclinical model of patient-derived cerebrospinal fluid circulating tumor cells for experimental therapeutics in leptomeningeal disease from melanoma.Neuro-oncology · 2022Article
- Network Pharmacology of Adaptogens in the Assessment of Their Pleiotropic Therapeutic Activity.Pharmaceuticals (Basel, Switzerland) · 2022Review
- IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells.Science signaling · 2022Article
- Protein kinase inhibitor ceritinib blocks ectonucleotidase CD39 - a promising target for cancer immunotherapy.Journal for immunotherapy of cancer · 2022Article
- Ceritinib is a novel triple negative breast cancer therapeutic agent.Molecular cancer · 2022Article
- Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.Molecular cancer · 2022Article
- EML4-ALK Variant 3 Promotes Mitotic Errors and Spindle Assembly Checkpoint Deficiency Leading to Increased Microtubule Poison Sensitivity.Molecular cancer research : MCR · 2022Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strategy, here we describe the anaplastic lymphoma kinase (ALK) inhibitor ceritinib as having activity across several ALK-negative lung cancer cell lines and identify new targets and network-wide signaling effects. Combining pharmacological inhibitors and RNA interference revealed a polypharmacology mechanism involving the noncanonical targets IGF1R, FAK1, RSK1 and RSK2. Mutating the downstream signaling hub YB1 protected cells from ceritinib. Consistent with YB1 signaling being known to cause taxol resistance, combination of ceritinib with paclitaxel displayed strong synergy, particularly in cells expressing high FAK autophosphorylation, which we show to be prevalent in lung cancer. Together, we present a systems chemical biology platform for elucidating multikinase inhibitor polypharmacology mechanisms, subsequent design of synergistic drug combinations, and identification of mechanistic biomarker candidates.
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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.