ArticleScientific reports2021
A proteomic platform to identify off-target proteins associated with therapeutic modalities that induce protein degradation or gene silencing.
Article in Scientific reports, 2021. 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
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Multi-Omics-Guided Design and Safety Engineering of Nucleic Acid Therapeutics: From Molecular Perturbation to Predictive Toxicology and Precision Translation.Chemical biology & drug design · 2026Review
- Safetyome and specialized panels for over 3,000 phenotypes: a systematic and translational approach using human genetics and pharmacology.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- A large-scale concordance study of toxicity findings across preclinical species and humans for small molecules and biologics.Frontiers in toxicology · 2026Article
- Protacs in cancer therapy: mechanisms, design, clinical trials, and future directions.Drug delivery and translational research · 2025Review
- Proteolysis-targeting chimeras with reduced off-targets.Nature chemistry · 2024Article
- Nano-Proteolysis Targeting Chimeras (Nano-PROTACs) in Cancer Therapy.International journal of nanomedicine · 2024Review
- Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.Journal of medicinal chemistry · 2023Review
- Review
- Review
- Targeted Protein Degradation: An Important Tool for Drug Discovery for "Undruggable" Tumor Transcription Factors.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel modalities such as PROTAC and RNAi have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate the abundance of off-target proteins. First, we selected off-target proteins using genetics and pharmacology evidence. This process yielded 2813 proteins, which we refer to as the "selected off-target proteome" (SOTP). An iterative algorithm was then used to identify four human cell lines out of 932. The 4 cell lines collectively expressed ~ 80% of the SOTP based on transcriptome data. Second, we used mass spectrometry to quantify the intracellular and extracellular proteins from the selected cell lines. Among over 10,000 quantifiable proteins identified, 1828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing to the rational selection process developed and the label free LC-MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.
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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.