ReviewTrends in pharmacological sciences2017
Leveraging Chemotype-Specific Resistance for Drug Target Identification and Chemical Biology.
Review in Trends in pharmacological sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed.
- A selective NVL inhibitor suppresses tumor growth by targeting ribosome biogenesis.Nature chemical biology · 2026Article
- Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting againstACS infectious diseases · 2025Article
- Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation.Molecular cancer · 2024Article
- Inducible mismatch repair streamlines forward genetic approaches to target identification of cytotoxic small molecules.Cell chemical biology · 2023Article
- Article
- Achieving the promise and avoiding the peril of chemical probes using genetics.Current opinion in structural biology · 2023Review
- High-content microscopy reveals a morphological signature of bortezomib resistance.bioRxiv : the preprint server for biology · 2023Article
- CRISPR-Suppressor Scanning for Systematic Discovery of Drug-Resistance Mutations.Current protocols · 2022Article
- enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Small Molecule Palmatine Targeting Musashi-2 in Colorectal Cancer.Frontiers in pharmacology · 2021Article
- Synthesis of 4-oxotetrahydropyrimidine-1(2H)-carboxamides derivatives as capsid assembly modulators of hepatitis B virus.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Article
- From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems.Molecules (Basel, Switzerland) · 2020Review
- Coibamide A Targets Sec61 to Prevent Biogenesis of Secretory and Membrane Proteins.ACS chemical biology · 2020Article
- Exploring Ovarian Cancer Cell Resistance to Rhenium Anticancer Complexes.Angewandte Chemie (International ed. in English) · 2020Article
- Exploring ovarian cancer cell resistance to rhenium anticancer complexes.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2020Article
- Chemical strategies to overcome resistance against targeted anticancer therapeutics.Nature chemical biology · 2020Review
- Distinct Mechanisms of Resistance to a CENP-E Inhibitor Emerge in Near-Haploid and Diploid Cancer Cells.Cell chemical biology · 2020Article
- Ploidy Leads a Molecular Motor to Walk Different Paths to Drug Resistance.Cell chemical biology · 2020Article
- Natural products as modulators of eukaryotic protein secretion.Natural product reports · 2020Review
- Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells.Chemical science · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Identifying the direct physiological targets of drugs and chemical probes remains challenging. Here we describe how resistance can be used to achieve 'gold-standard' validation of a chemical inhibitor's direct target in human cells. This involves demonstrating that a silent mutation in the target that suppresses inhibitor activity in cell-based assays can also reduce inhibitor potency in biochemical assays. Further, phenotypes due to target inhibition can be identified as those observed in the inhibitor-sensitive cells, across a range of inhibitor concentrations, but not in genetically matched cells with a silent resistance-conferring mutation in the target. We propose that chemotype-specific resistance, which is generally considered to be a limitation of molecularly targeted agents, can be leveraged to deconvolve the mechanism of action of drugs and to properly use chemical probes.
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Registered trials
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