ArticleMolecular systems biology2015
A chemical-genetic interaction map of small molecules using high-throughput imaging in cancer cells.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed.
- Review
- A human metabolic map of pharmacological perturbations reveals drug modes of action.Nature biotechnology · 2025Article
- Article
- The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype, promoting a favorable response to anti-PD-1 therapy via NLRP3 activation.Cellular & molecular immunology · 2024Article
- Computer-Aided Drug Design and Drug Discovery: A Prospective Analysis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Targeting pan-essential pathways in cancer with cytotoxic chemotherapy: challenges and opportunities.Cancer chemotherapy and pharmacology · 2023Review
- NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases.Life (Basel, Switzerland) · 2022Review
- High-dimensional gene expression and morphology profiles of cells across 28,000 genetic and chemical perturbations.Nature methods · 2022Article
- Pooled genetic screens with image-based profiling.Molecular systems biology · 2022Review
- Multiparametric High-Content Cell Painting Identifies Copper Ionophores as Selective Modulators of Esophageal Cancer Phenotypes.ACS chemical biology · 2022Article
- The drug-induced phenotypic landscape of colorectal cancer organoids.Nature communications · 2022Article
- Application of Artificial Intelligence in Discovery and Development of Anticancer and Antidiabetic Therapeutic Agents.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- A Network-Guided Approach to Discover Phytochemical-Based Anticancer Therapy: Targeting MARK4 for Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- C-MORE: A high-content single-cell morphology recognition methodology for liquid biopsies toward personalized cardiovascular medicine.Cell reports. Medicine · 2021Article
- Image-based profiling for drug discovery: due for a machine-learning upgrade?Nature reviews. Drug discovery · 2021Review
- Morphological Profiling Identifies a Common Mode of Action for Small Molecules with Different Targets.Chembiochem : a European journal of chemical biology · 2020Article
- Predicting Drug Response and Synergy Using a Deep Learning Model of Human Cancer Cells.Cancer cell · 2020Article
- Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis.Scientific reports · 2020Article
- LingZhi oligopeptides amino acid sequence analysis and anticancer potency evaluation.RSC advances · 2020Article
- High Content Analysis Across Signaling Modulation Treatments for Subcellular Target Identification Reveals Heterogeneity in Cellular Response.Frontiers in cell and developmental biology · 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
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small molecules often affect multiple targets, elicit off-target effects, and induce genotype-specific responses. Chemical genetics, the mapping of the genotype dependence of a small molecule's effects across a broad spectrum of phenotypes can identify novel mechanisms of action. It can also reveal unanticipated effects and could thereby reduce high attrition rates of small molecule development pipelines. Here, we used high-content screening and image analysis to measure effects of 1,280 pharmacologically active compounds on complex phenotypes in isogenic cancer cell lines which harbor activating or inactivating mutations in key oncogenic signaling pathways. Using multiparametric chemical-genetic interaction analysis, we observed phenotypic gene-drug interactions for more than 193 compounds, with many affecting phenotypes other than cell growth. We created a resource termed the Pharmacogenetic Phenome Compendium (PGPC), which enables exploration of drug mode of action, detection of potential off-target effects, and the generation of hypotheses on drug combinations and synergism. For example, we demonstrate that MEK inhibitors amplify the viability effect of the clinically used anti-alcoholism drug disulfiram and show that the EGFR inhibitor tyrphostin AG555 has off-target activity on the proteasome. Taken together, this study demonstrates how combining multiparametric phenotyping in different genetic backgrounds can be used to predict additional mechanisms of action and to reposition clinically used drugs.
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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.