ArticleChemical science2022
Highly effective identification of drug targets at the proteome level by pH-dependent protein precipitation.
Article in Chemical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Peptide-centric local stability assay (PELSA) for sensitive identification of ligand-targeting proteins and binding sites at proteome scale.Nature protocols · 2026Review
- Recent advances in proteomic strategies for target identification of traditional Chinese medicine.Journal of pharmaceutical analysis · 2026Review
- An approach for the systematic profiling of drug-induced remodeling of RNA-RBP (RNA-binding protein) interactions.RSC advances · 2026Article
- Copper Transporter 1‑Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.ACS pharmacology & translational science · 2026Article
- Label-Free Target Discovery Strategy for Natural Active Products.Biomolecules · 2026Review
- Proteome-Wide Monitoring of Drug Action in Living Cells Using a Novel Label-Free Solvent-Based Shift Assay.Molecular & cellular proteomics : MCP · 2025Article
- Solvent-induced partial cellular fixation decodes proteome-wide drug targets and downstream pathways in living cells.Nature communications · 2025Article
- Kinome analysis of Madurella mycetomatis identified kinases in the cell wall integrity pathway as novel potential therapeutic drug targets in eumycetoma caused by Madurella mycetomatis.PLoS neglected tropical diseases · 2025Article
- Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.Exploration (Beijing, China) · 2025Review
- Extrinsic and intrinsic factors affect copper-induced protein precipitation across eukaryotic and prokaryotic proteomes.Protein science : a publication of the Protein Society · 2025Article
- [Recent advances in protein precipitation-based methods for drug-target screening].Se pu = Chinese journal of chromatography · 2024Review
- [Identification of the binding proteins of organic acid metabolites by matrix thermal shift assay].Se pu = Chinese journal of chromatography · 2024Article
- Stability-based approaches in chemoproteomics.Expert reviews in molecular medicine · 2024Review
- A strategy to disentangle direct and indirect effects on (de)phosphorylation by chemical modulators of the phosphatase PP1 in complex cellular contexts.Chemical science · 2024Article
- The Introduction of Detergents in Thermal Proteome Profiling Requires Lowering the Applied Temperatures for Efficient Target Protein Identification.Molecules (Basel, Switzerland) · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fully understanding the target spaces of drugs is essential for investigating the mechanism of drug action and side effects, as well as for drug discovery and repurposing. In this study, we present an energetics-based approach, termed pH-dependent protein precipitation (pHDPP), to probe the ligand-induced protein stability shift for proteome-wide drug target identification. We demonstrate that pHDPP works for a diverse array of ligands, including a folate derivative, an ATP analog, a CDK inhibitor and an immunosuppressant, enabling highly specific identification of target proteins from total cell lysates. This approach is compared to thermal and solvent-induced denaturation approaches with a pan-kinase inhibitor as the model drug, demonstrating its high sensitivity and high complementarity to other approaches. Dihydroartemisinin (DHA), a dominant derivative of artemisinin to treat malaria, is known to have an extraordinary effect on the treatment of various cancers. However, the anti-tumor mechanisms remain unknown. pHDPP was applied to reveal the target space of DHA and 45 potential target proteins were identified. Pathway analysis indicated that these target proteins were mainly involved in metabolism and apoptosis pathways. Two cancer-related target proteins, ALDH7A1 and HMGB1, were validated by structural simulation and AI-based target prediction methods. And they were further validated to have strong affinity to DHA by using cellular thermal shift assay (CETSA). In summary, pHDPP is a powerful tool to construct the target protein space to reveal the mechanism of drug action and would have broad application in drug discovery studies.
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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.