ArticleCell chemical biology2019
Divergent Polypharmacology-Driven Cellular Activity of Structurally Similar Multi-Kinase Inhibitors through Cumulative Effects on Individual Targets.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 18 citations in OpenAlex.
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- Fatty acid-binding protein 4 as a biomarker for colon adenocarcinoma risk and prognosis: Challenges and future directions.World journal of gastrointestinal oncology · 2025Article
- 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
- PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis.Cancer research · 2024Article
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Turning liabilities into opportunities: Off-target based drug repurposing in cancer.Seminars in cancer biology · 2021Review
- TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors.Cancer discovery · 2021Article
- Lowering Sample Requirements to Study Tyrosine Kinase Signaling Using Phosphoproteomics with the TMT Calibrator Approach.Proteomics · 2020Article
- Cyclin-Dependent Kinase 5 Inhibitor Butyrolactone I Elicits a Partial Agonist Activity of Peroxisome Proliferator-Activated Receptor γ.Biomolecules · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Despite recent successes of precision and immunotherapies there is a persisting need for novel targeted or multi-targeted approaches in complex diseases. Through a systems pharmacology approach, including phenotypic screening, chemical and phosphoproteomics, and RNA-seq, we elucidated the targets and mechanisms underlying the differential anticancer activity of two structurally related multi-kinase inhibitors, foretinib, and cabozantinib, in lung cancer cells. Biochemical and cellular target validation using probe molecules and RNAi revealed a polypharmacology mechanism involving MEK1/2, FER, and AURKB, which were each more potently inhibited by foretinib than cabozantinib. Based on this, we developed a synergistic combination of foretinib with barasertib, a more potent AURKB inhibitor, for MYC-amplified small-cell lung cancer. This systems pharmacology approach showed that small structural changes of drugs can cumulatively, through multiple targets, result in pronounced anticancer activity differences and that detailed mechanistic understanding of polypharmacology can enable repurposing opportunities for cancers with unmet medical need.
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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.