ArticleJournal of medicinal chemistry2020
Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications.
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 143 citations in OpenAlex.
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.Journal of medicinal chemistry · 2026Article
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Enzyme-Induced Supramolecular Proteolysis-Targeting Chimeras Enable Tumor-Targeted Protein Degradation.JACS Au · 2026Article
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.bioRxiv : the preprint server for biology · 2026Article
- SCaN: A Screening and Characterization Platform for Nanosuspensions Enables In Vivo Delivery of a Crystalline hRpn13ACS pharmacology & translational science · 2026Article
- Click. Screen. Degrade. A Miniaturized D2B Workflow for Rapid PROTAC Discovery.Journal of medicinal chemistry · 2026Article
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- MolGlueDB: an online database of molecular glues.Nucleic acids research · 2026Article
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- Photocontrolled trimethoprim PROTACs targeting the eDHFR protein tag.Nature communications · 2025Article
- Machine Learning-Assisted False Positive Detection in Metabolite Identification Workflows.Analytical chemistry · 2025Article
- Second-Generation AURKA-Targeting PROTACs: Structural Optimization toward in Vivo Degradation in Neuroblastoma.Journal of medicinal chemistry · 2025Article
- Design, Optimization, and Development of RIPK1 Degraders with Improved Pharmacokinetic and Pharmacodynamic Properties.Journal of medicinal chemistry · 2025Article
- Dual functionality of MDM2 in PROTACs expands the horizons of targeted protein degradation.Biomarker research · 2025Review
- Linker Methylation as a Strategy to Enhance PROTAC Oral Bioavailability: Insights from Molecular Properties and Conformational Analysis.Journal of medicinal chemistry · 2025Article
- Unveiling New Triazoloquinoxaline-Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Characterization of preclinical radio ADME properties of ARV-471 for predicting human PK using PBPK modeling.Journal of pharmaceutical analysis · 2025Article
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hetero-bifunctional PROteolysis TArgeting Chimeras (PROTACs) represent a new emerging class of small molecules designed to induce polyubiquitylation and proteasomal-dependent degradation of a target protein. Despite the increasing number of publications about the synthesis, biological evaluation, and mechanism of action of PROTACs, the characterization of the pharmacokinetic properties of this class of compounds is still minimal. Here, we report a study on the metabolism of a series of 40 PROTACs in cryopreserved human hepatocytes at multiple time points. Our results indicated that the metabolism of PROTACs could not be predicted from that of their constituent ligands. Their linkers' chemical nature and length resulted in playing a major role in the PROTACs' liability. A subset of compounds was also tested for metabolism by human cytochrome P450 3A4 (CYP3A4) and human aldehyde oxidase (
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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.