ArticleNature chemical biology2018
A whole-animal platform to advance a clinical kinase inhibitor into new disease space.
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 44 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
44 citing papers in PubMed, 71 citations in OpenAlex.
- An Unbiased Drug Screen in a Drosophila Model ofInternational journal of molecular sciences · 2026Article
- Genotype-Informed Whole-Animal Kinome Screening Reveals Shared Kinase Vulnerabilities Across Driver Contexts in PDAC.Cancer science · 2026Article
- Chemical programming of kinase inhibitors in a modular chemputer-based system.Communications biology · 2026Article
- Exploring the versatility ofFly · 2025Review
- Stress-induced organismal death is genetically regulated by the mTOR-Zeste-Phae1 axis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of NAD-GPx4 axis and MEK triggers ferroptosis to suppress pancreatic ductal adenocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A stress-responsive p38 signaling axis in choanoflagellates.RSC chemical biology · 2025Article
- Article
- Modelling Cancer in Drosophila: Exploration to Personalised Medicine.Advances in experimental medicine and biology · 2025Review
- Functional exploration of copy number alterations in a Drosophila model of triple-negative breast cancer.Disease models & mechanisms · 2024Article
- Concurrent targeting of GSK3 and MEK as a therapeutic strategy to treat pancreatic ductal adenocarcinoma.Cancer science · 2024Article
- Polyploid Cancer Cell Models in Drosophila.Genes · 2024Review
- WNTinib is a multi-kinase inhibitor with specificity against β-catenin mutant hepatocellular carcinoma.Nature cancer · 2023Article
- Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility.Nature communications · 2023Article
- A targeted genetic modifier screen in Drosophila uncovers vulnerabilities in a genetically complex model of colon cancer.G3 (Bethesda, Md.) · 2023Article
- A Drosophila chemical screen reveals synergistic effect of MEK and DGKα inhibition in Ras-driven cancer.Disease models & mechanisms · 2023Article
- Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System.ChemMedChem · 2022Article
- Bioluminescent Zebrafish Transplantation Model for Drug Discovery.Frontiers in pharmacology · 2022Article
- Review
- Crowdsourced identification of multi-target kinase inhibitors for RET- and TAU- based disease: The Multi-Targeting Drug DREAM Challenge.PLoS computational biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Synthetic tailoring of approved drugs for new indications is often difficult, as the most appropriate targets may not be readily apparent, and therefore few roadmaps exist to guide chemistry. Here, we report a multidisciplinary approach for accessing novel target and chemical space starting from an FDA-approved kinase inhibitor. By combining chemical and genetic modifier screening with computational modeling, we identify distinct kinases that strongly enhance ('pro-targets') or limit ('anti-targets') whole-animal activity of the clinical kinase inhibitor sorafenib in a Drosophila medullary thyroid carcinoma (MTC) model. We demonstrate that RAF-the original intended sorafenib target-and MKNK kinases function as pharmacological liabilities because of inhibitor-induced transactivation and negative feedback, respectively. Through progressive synthetic refinement, we report a new class of 'tumor calibrated inhibitors' with unique polypharmacology and strongly improved therapeutic index in fly and human MTC xenograft models. This platform provides a rational approach to creating new high-efficacy and low-toxicity drugs.
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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.