ArticleJournal of medicinal chemistry2023
Physicochemical Property Determinants of Oral Absorption for PROTAC Protein Degraders.
Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 128 citations in OpenAlex.
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- From prediction to performance:International journal of pharmaceutics: X · 2026Article
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Harnessing the ubiquitin-proteasome system: advances and challenges of PROTACs in breast cancer.Molecular biology reports · 2026Review
- Limiting Trial-and-Error: Linker-Based 2D Descriptor Analysis to Support Very Early Proteolysis-Targeting Chimeras Design.ChemMedChem · 2026Article
- Toward Rational Design of Orally Bioavailable PROTACs: Development of a Fully Computational Oral Absorption Score.ACS medicinal chemistry letters · 2026Article
- DesignMaster: a multi-conditional diffusion framework for rational PROTAC design.Bioinformatics (Oxford, England) · 2026Article
- A design approach for bitopic kinase inhibitors.Nature · 2026Article
- Proteolysis Targeting Chimera (PROTAC) Linkerology Enhances the CDK-Degradation Selectivity Profile of a Multi-CDK Inhibitor: Discovery of Potent, Anti-Leukemic CDK9 Degraders.ACS pharmacology & translational science · 2026Article
- Delivering Degradation: Nanomedicine and Programmable Proximity Platforms for Targeted Protein Degradation.Pharmaceutics · 2026Review
- Daraxonrasib and Beyond: Pan-RAS Inhibition, Resistance, and Next-Generation Strategies.Cancer science · 2026Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- AKR1C3 inhibitors and exploiters for the treatment and therapeutic monitoring of cancer: a patent review (2020-present).Expert opinion on therapeutic patents · 2026Review
- Design of Synthesizable PROTACs through Synthesis Constrained Generative Model and Reinforcement Learning.JACS Au · 2026Article
- FDA Approval of the First-Ever PROTAC: Vepdegestrant (ARV-471) Marks a New Era in Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.Journal of medicinal chemistry · 2026Article
- Pyridine-containing antitumor agents: structure-oriented medicinal chemistry, structure-activity relationships, and ADMET liabilities.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Research Trends and Emerging Frontiers in Proteolysis Targeting Chimeras (PROTACs): A Bibliometric Analysis of 2630 Publications (2001-2025).Pharmaceuticals (Basel, Switzerland) · 2026Article
- Development of TSSK1 and TSSK2 Targeted Degraders Reveals Sperm Machinery for Protein Degradation and Potential for Nonhormonal Male Contraception.Journal of medicinal chemistry · 2026Article
- The In Vivo Effect of Amorphous Drug Nanoprecipitates on the Intestinal Absorption of the PROTACs ARV-110 (Bavdeglutamide) and ARV-471 (Vepdegestrant).Molecular pharmaceutics · 2026Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterobifunctional PROTAC degraders are gaining attention as a differentiated therapeutic modality with the potential for oral dosing in the clinic. Belonging to the beyond Rule of Five domain of physicochemical property space, we have sought to understand the determinants of oral absorption for this class of molecules for the rapid development of novel oral agents. We have collected a large data set from PROTAC molecules that have been dosed orally and intravenously in rats to estimate the fraction absorbed from oral dosing. Through this estimation, effects from differential hepatic clearance are normalized, allowing for a better assessment of the absorption. We demonstrate that rats are less permissive to PROTAC absorption than mice. The physicochemical properties of the molecules are then evaluated once compounds are rank-ordered by the fraction absorbed. We derive suggested design constraints on physicochemical properties for PROTAC molecules that are associated with higher probability of being orally absorbed.
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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.