ArticleACS medicinal chemistry letters2022
Direct-to-Biology Accelerates PROTAC Synthesis and the Evaluation of Linker Effects on Permeability and Degradation.
Article in ACS medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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
69 citing papers in PubMed, 138 citations in OpenAlex.
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- High-throughput reaction screening using acoustic ejection mass spectrometry.Nature protocols · 2026Review
- Accelerate Your Science: Direct-to-Biology Strategies in Medicinal Chemistry.Journal of medicinal chemistry · 2026Review
- A Direct-to-Biology Amine-Acid Amination for Rapid Phenotypic Profiling of Lysosomotropic Natural Products.Journal of the American Chemical Society · 2026Article
- A Plug-and-Play Platform for Customizing Multivalent Degraders and Degrader-Drug Conjugates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Assays for Measuring the Cell Permeability of Proteolysis-Targeting Chimeras (PROTACs): Performance, Correlations, Applicability and Recommendations.Molecular pharmaceutics · 2026Article
- Early-stage drug discovery in a new-generation ultrahigh-throughput mass spectrometry platform.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development of a Direct-to-Biology Platform to Discover Potent MNK Inhibitors.Journal of medicinal chemistry · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Mapping the avoid-ome: a systematic open-science approach to predictive ADMET.Nature communications · 2026Review
- Proteolysis-targeting chimera (PROTAC) in cancer: design principles and applications on "undruggable" targets.Biomarker research · 2026Review
- Black-box data: a new paradigm for biomedicine in the AI era.Chemical science · 2026Review
- Advances in BRET probes for intracellular target engagement studies.Nature chemical biology · 2026Review
- Nanoscale Direct-to-Biology Optimization of Cdk2 Inhibitors.Journal of medicinal chemistry · 2026Article
- Alkyne Two-Phase Strategy: Rapid Generation of TK-285-Derived PROTACs as BRD4 Degraders.Journal of medicinal chemistry · 2026Article
- Systematic Optimization of Proteolysis-Targeting Chimeras for PIN1 Enables Selective Degradation and Antitumor Activity In Vivo.Pharmaceutics · 2026Article
- Direct-to-Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery.ChemMedChem · 2026Review
- 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
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) has been developed using a direct-to-biology (D2B) approach with a focus on linker effects. A large number of linker analogs-with varying length, polarity, and rigidity-were rapidly prepared and characterized in four cell-based assays by streamlining time-consuming steps in synthesis and purification. The expansive dataset informs on linker structure-activity relationships (SAR) for in-cell E3 ligase target engagement, degradation, permeability, and cell toxicity. Unexpected aspects of linker SAR was discovered, consistent with literature reports on "linkerology", and the method dramatically speeds up empirical optimization. Physicochemical property trends emerged, and the platform has the potential to rapidly expand training sets for more complex prediction models. In-depth validation studies were carried out and confirm the D2B platform is a valuable tool to accelerate PROTAC design-make-test cycles.
Identifiers
What OpenQuestion holds
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.