RESEARCH PAPER: Combinatorial use of VHL and KEAP1 PROTACs reveals unexpected synergy and hook effect relief
By Islam et al., and Luca Busino
➡️ https://genesdev.cshlp.org/content/40/5-6/308.abstract

Penn Medicine
#PROTAC #KRAS #cancer #cancertherapy

🧬 Sharing an #openacces review that highlights how chemoinformatics, molecular modeling, structural bioinformatics, and machine learning are accelerating the design of protein degraders. 👉
doi.org/10.1016/j.dr...

#PROTAC #DrugDiscovery #Chemoinformatics #ComputationalChemistry

Join us at the 6th TPD & Induced Proximity Summit Europe and Induced Proximity Summit in London, 10 to 12 March 2026, which brings together experts to explore the latest advancements in targeted protein degradation.

We look forward to seeing you there!

#PROTAC #TPD #DrugDiscovery

Researchers overcome major obstacle in targeted protein degradation Researchers overcome major obstacle in targeted protein degradation

Breakthrough Aurora A PROTAC on the Chemical Probes Portal ⭐⭐⭐⭐

CCT400028 @icr.ac.uk London overcomes the hook effect, delivers >120h stability, is highly selective, and includes a matched inactive control.

Powering paediatric cancer research.
#ChemicalProbes #PROTAC

Read more 👇

Chimera Crosses Blood-Brain Barrier to Degrade mHTT Aggregates in Huntington Disease A compound with therapeutic potential in Huntington disease (HD) preferentially degrades mHTT aggregates and improves survival in model mice.

As reported in the @jacs.acspublications.org researchers demonstrated that a proteolysis-targeting chimera (#PROTAC) penetrates the brain to preferentially degrade mutant huntingtin (#mHTT) aggregates in #HuntingtonDisease (HD) mice.

Read here: https://bit.ly/4kTKS5d

#RareDisease #MedSky

🆕 ADVANCE ONLINE 🆕

RESEARCH PAPER: Combinatorial use of VHL and KEAP1 PROTACs reveals unexpected synergy and hook effect relief
By Islam et al., and Luca Busino
➡️ genesdev.cshlp.org/content/early/2025/12/08...


#PROTAC #KRAS #cancer #cancertherapy

✨Research spotlight on targeted protein degraders: from macrocyclic peptides to nanoparticle-based delivery systems, there is a wealth and diversity of PROTACs research published in #RSCChemBio each year.
Find the highlights from 2025 on our blog now:
🔗blogs.rsc.org/cb/202...
#PROTAC #RSCChemBio

The PROTAC Market: Accelerated Growth and Innovations in Targeted Therapy (2025-2034) The PROTAC market is rapidly expanding, driven by the growing demand for targeted therapies. Discover key players, market potential, and the drugs redefining treatment strategies.

The PROTAC Market: Accelerated Growth and Innovations in Targeted Therapy (2025-2034) #Las_Vegas #Arvinas #Pfizer #PROTAC

#TargetedProteinDegradation #InducedProximity #MolecularGlue #TPD #eTPD #PROTAC #LYTAC #MoDEA #KineTAC #PROTAB #AbTAC #EpiTAC #REULR #GlueTAC #TICTAC #AUTAC #ATTEC #AUTOTAC #TrogoTAC #RIPR #RIPTAC #AgnoTAC #FragTAC #SHEDTAC

PZ Nachgefragt: Weltkrebstag und PROTAC Anlässlich des Weltkrebstags blicken die Professoren Dr. Theo Dingermann und Dr. Manfred Schubert-Zsilavecz im PZ-Podcast auf die neue Arzneistof...

Anlässlich des #Weltkrebstags blicken die beiden Professoren Dr. Theo Dingermann und Dr. Manfred Schubert-Zsilavecz in der neuen Folge des PZ-Podcasts auf die neue Arzneistoffklasse der #PROTAC, die künftig Versorgungslücken bei bestimmten Krebsarten schließen könnte.

Diastereomeric Branched-Ester dBET1 Analogs Exhibit Conformation-Dependent Differences in Passive Membrane Permeability Proteolysis-targeting chimeras (PROTACs) represent a promising therapeutic modality, but their clinical translation is often hindered by poor pharmacokinetic properties associated with their location in the “beyond Rule of 5” chemical space. Using the BRD4 degrader dBET1 as a model, this study explored a dual approach to improve the cellular permeability of PROTACs by combining amide-to-ester substitution with the strategic linker methylation to induce stereochemistry-driven conformational modulation. Substitution with ester enhanced both permeability and degradation potency, while methylation afforded two diastereomers with different permeability profiles. Steered molecular dynamics and enhanced conformational sampling in polar and nonpolar environments revealed distinct chameleonic behaviors, with the more permeable diastereomer 2b adopting folded conformations with a lower solvent-accessible 3D polar surface area in the nonpolar environment. These findings were supported by 2D NMR and hydrogen-bond acidity analyses (ANMR). Notably, low-energy “congruent conformation” accessible in both environments was identified for 2b. This work establishes a viable strategy for the design of membrane-permeable PROTACs.

Latest paper in J. Med. Chem. @pubs.acs.org ! We discovered that #PROTAC diastereomers exhibit different membrane permeability, driven by their distinct chameleonicity.🦎

Congrats to Mazin, Eisuke, and Keigo on this great work!

Check it out: pubs.acs.org/doi/10.1021/...

E3 Ubiquitin Ligases: Structures, Biological Functions, Diseases, and Therapy E3 ligases function as critical regulators of cellular protein degradation, and their dysregulation is a core pathogenic mechanism in a wide array of human diseases, including cancer, cardiovascular ...

#Article in #MedComm

E3 Ubiquitin Ligases: Structures, Biological Functions, Diseases, and Therapy doi.org/10.1002/mco2...

#cancer #E3_UbiquitinLigase #AD #PD #PROTAC #TPD

Successful Development of Efficient Synthesis Method for PROTACs Through Consecutive Click Reactions A groundbreaking method for synthesizing PROTACs efficiently has been developed using consecutive click reactions, promising rapid advancements in drug research.

Successful Development of Efficient Synthesis Method for PROTACs Through Consecutive Click Reactions #Japan #Tokyo #Tokyo_University #PROTAC #SYNTHEM

新たな創薬の可能性を拓く！PROTACの効率的合成法が開発される 東京理科大学の研究チームが、PROTACの効率的な合成手法を確立しました。新たな医薬品開発の大きな一歩となるこの研究に期待が寄せられています。

新たな創薬の可能性を拓く！PROTACの効率的合成法が開発される #PROTAC #クリック反応 #創薬研究

東京理科大学の研究チームが、PROTACの効率的な合成手法を確立しました。新たな医薬品開発の大きな一歩となるこの研究に期待が寄せられています。

創薬の未来を変える！PROTAC合成の新手法が登場 東京理科大学の研究チームが、PROTACの効率的合成手法を開発しました。新しい連続クリック反応技術で、創薬研究の加速が期待されています。

創薬の未来を変える！PROTAC合成の新手法が登場 #東京理科大学 #創薬 #PROTAC

東京理科大学の研究チームが、PROTACの効率的合成手法を開発しました。新しい連続クリック反応技術で、創薬研究の加速が期待されています。

Negative Impact of p21‐Activated Kinase 4‐Mediated AMP‐Activated Protein Kinase Inhibition on Sarcopenia in Mice and Humans PAK4 is overexpressed in muscle atrophy and negatively correlates with muscle mass and function in humans. Inhibiting PAK4 activates AMPK/PGC-1α-driven mitochondrial biogenesis by blocking AMPKα2-S4...

#Article in #MedComm
Negative Impact of p21-Activated Kinase 4-Mediated AMP-Activated Protein Kinase Inhibition on Sarcopenia in Mice and Humans doi.org/10.1002/mco2...

#AMPK #mitochondria #MuscleAtrophy #PAK4 #PROTAC

Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation O=C(N1)[C@@H](NC2=CC=C(N3CCN(C4COC5(CCN(C6=NC=C(C7=CC8=C(N=C[C@@]([C@@]9=C(C)C=CC(O)=C9C)=C8C#N)N7)C=N6)CC5)C4)CC3)C(F)=C2)CCC1=O Yazhou Wang et al. Nature Communication 16, 10759 (2025) 10.1038/s41467-025-65796-8

PKMYT1 is a promising target for #cancer #drug developmenent. While some inhibitors such as RP-6036 are available for some time, researchers from InSilico #Medicine have now introduced a novel #PROTAC degrader based on their computational design of a novel […]

[Original post on mstdn.social]

December 2025.
Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation
Doi: doi.org/10.1002/ddr....
#WILEY
#Drug_Development_Research
#PROTAC #Oncology

Targeted therapies for #HPVrelated #cancers are greatly needed. The development of an E6-targeting #PROTAC degrade the #HPV viral oncogene and inhibits HPV+ tumor growth through tumor-intrinsic and immunomodulatory effects ➡️ bit.ly/4oAwSxu

Highlights summarized below ⬇️

@moffittnews.bsky.social

Predicting PROTAC off-target effects via warhead involvement levels in drug–target interactions using graph attention neural networks. Computational and Structural Biotechnology Journal, DOI: https://doi.org/10.1016/j.csbj.2025.10.028

🔗 Predicting PROTAC off-target effects via warhead involvement levels in drug–target interactions using graph attention neural networks. Computational and Structural Biotechnology Journal, DOI: doi.org/10.1016/j.cs...

📚 CSBJ: www.csbj.org

#StructuralBiology #ChemicalBiology #PROTAC #DrugDiscovery

🔬 In PROTAC and molecular-glue research, verifying mechanism of action is essential to confirm E3 recruitment.

Absea’s Pullroven® IP-MS-validated E3 antibodies deliver mass-spec-grade readouts of E3 enrichment for confident mechanistic validation.

#PROTAC #TPD

For my first post, a big thank you to @alessiociulli.bsky.social
Really enjoyed your seminar yesterday on #TPD #PROTAC and Intermolecular Bivalent Glues. Such an exciting time for this field!

🚀 New J. Med. Chem. study: Linker methylation boosts oral bioavailability of VHL-PROTACs.
📊 #alvaDesc linked chemical space to PK for smarter design in #bRo5.

📄 Read the paper: doi.org/10.1021/acs....
🔗 Check alvaDesc at: alvascience.com/alvadesc/

#DrugDiscovery #PROTAC #ADME #chemsky

There's till time to talk to our rep in Cambridge and find out how Fluorochem can support your ADC and PROTAC synthesis, library development or custom projects!🧪

#CamMedChem25 #ADC #PROTAC #Pharma #ChemSky #BioSky #AcademicSky

We offer several thalidomide analog-based ligands that feature C-C sp3 linkages, among other degrader linkers. Explore our catalog with easy ways to purchase:
- request a direct quote
- through our online shop
- find us on eMolecules

#KnightChem #PROTAC #medchem #synchem

Mapping the energy landscape of PROTAC-mediated protein-protein interactions. Computational and Structural Biotechnology Journal, DOI: https://doi.org/10.1016/j.csbj.2023.02.049

🧩 The future of drug discovery may depend on how well we understand PROTAC-driven protein partnerships.

🔗 Mapping the energy landscape of PROTAC-mediated protein-protein interactions. Computational and Structural Biotechnology Journal, DOI: doi.org/10.1016/j.cs...

📚 CSBJ: www.csbj.org

#PROTAC #AI

Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase - PubMed The bifunctional soluble epoxide hydrolase (sEH) represents a promising target for inflammation-related diseases. Although potent inhibitors targeting each domain are available, sEH-PROTACs offer the ...

🚀 New paper out! 🚀

TACTIC Team with other researchers designed PROTACs that degrade soluble epoxide hydrolase (sEH) using a structure-based approach.

Check it out 👉 (pubmed.ncbi.nlm.nih.gov/40532036/)

#PROTAC #DrugDiscovery #StructuralBiology

In this study, scientists developed and evaluated a Von Hippel-Lindau (VHL)-recruiting METTL3 #PROTAC, ZW27941, which effectively degrades METTL3 and demonstrates enhanced #AntiLeukemicActivity. #AML #medsky
#OpenAccess: www.sciencedirect.com/science/arti...

PROTAC Clinical Achievement: New Oral Estrogen Receptor Degrader Shows Promise in Advanced Breast Cancer the VERITAC-2 phase 3 trial in patients with ER-positive, HER2-negative advanced breast cancer found that vepdegestrant (ARV-471), an oral PROTAC estrogen receptor degrader, achieved significantly lon...

PROTAC Clinical Achievement: New Oral Estrogen Receptor Degrader Shows Promise in Advanced Breast Cancer

www.marinbio.com/protac-clini...

#protac #breastcancer

AI Breakthrough By UW Scientists Targets ‘Undruggable’ Proteins, Paving Path to Novel Therapies For decades, a significant portion of human biology — estimated at around 85% of all proteins — has remained frustratingly out of reach…

AI Breakthrough By UW Scientists Targets ‘Undruggable’ Proteins, Paving Path to Novel Therapies.

#UndruggableNoMore, #AIDrugDiscovery, #PROTAC, #TargetedProteinDegradation, #UWMedicine, #CancerTherapy, #AlzheimersResearch, #MedicalBreakthrough,

medium.com/@jckapadia00...