Highlighted Publications

Provides a comprehensive framework for evaluating and mitigating safety risks associated with CRBN-based degraders.

Community-driven recommendations and best practices for advancing CRBN degrader programs safely into clinical development.

Provides important insight into how tumors adapt to prolonged degrader treatment.

Targeted degradation of KRASG12V identified resistance mechanisms that emerge during chronic treatment.

Provides a comprehensive overview of how molecular glues can be used for both degradation and non-degrading functional modulation.

Review covering degrading and non-degrading molecular glues and the expanding scope of glue-mediated biology.

Expands induced proximity into covalent space and opens opportunities for discovering new functional protein interactions.

COUPLrs use two covalent warheads to create proximity between proteins through irreversible engagement.

Provides a blueprint for advancing bifunctional degraders from discovery through clinical development.

Describes the medicinal chemistry optimization and progression of a clinical-stage androgen receptor degrader.

Demonstrates that induced proximity can reprogram transcriptional networks without requiring degradation, expanding therapeutic opportunities beyond traditional TPD.

Recruitment of CBP/EP300 to BCL6 drives transcriptional rewiring and cancer cell death.

Highlights the power of direct-to-biology workflows to accelerate degrader discovery and SAR exploration.

D2B screening rapidly identified active CRBN-based HaloPROTAC degraders.

Demonstrates that even highly challenging and short-lived targets such as c-Myc may be degradable when paired with the right ligase.

Systematic BioPROTAC screening identified productive E3 ligase combinations capable of degrading c-Myc.

Demonstrates how molecular glue stabilization can unlock entirely new degradation mechanisms and expand the target space of degraders.

Molecular glue stabilizers were combined with PROTAC design to induce degradation of estrogen receptor through its complex with 14-3-3.

Establishes native MS as a powerful analytical approach for studying increasingly complex induced-proximity systems.

Native mass spectrometry was applied to characterize PROTAC ternary complexes, including CRL2(VHL)-based assemblies.

Shows the growing potential of TCIPs to modulate transcription factor biology through proximity-induced functional reprogramming.

Development and optimization of BCL6-BRD4 TCIPs capable of altering target-driven transcriptional programs.

Expands understanding of CRBN-mediated molecular glue mechanisms and demonstrates new structural solutions for target engagement.

Discovery of an unexpected ternary complex architecture enabling degradation of KAT2A without a classical G-loop interaction.

Introduces a new induced proximity modality for engineering immune-cell-specific protein degradation.

TICTACs use CD206 targeting on tumor-associated macrophages to selectively remove immune checkpoint receptors.

Demonstrates that a single bifunctional molecule can engage multiple degradation pathways simultaneously.

CRBN is targeted directly to the proteasome via a ByeTAC mechanism while Rpn13 is degraded through CRBN-mediated ubiquitination.

Provides a deeper mechanistic understanding of how ER degraders drive therapeutic activity beyond receptor loss.

Reveals contributions of chromatin trapping, SUMOylation, transcriptional repression, and ER degradation to SERD activity.

Provides mechanistic insight into ternary complex formation for a clinically relevant degrader and helps reveal the structural principles underlying productive degradation.

Cryo-EM characterization of the CRBN-IRAK4 degrader ternary complex reveals how structure drives degradation efficiency.

Illustrates how small changes in chemistry can dramatically alter a molecule's mode of action.

Conversion of kinase inhibitors into stabilizers and ultimately degraders through covalent warhead incorporation and linker optimization.

Extends targeted protein degradation beyond human biology into infectious disease and bacterial systems.

First report of a small-molecule bacterial proteolysis targeting chimera capable of degrading Mycobacterium tuberculosis proteins.

Predicting oral bioavailability remains one of the biggest challenges in degrader drug discovery.

Introduces modeling approaches to understand and predict oral exposure of beyond-Rule-of-Five molecules.

Provides practical guidance for selecting degron systems in biological and translational studies.

Systematic comparison of degron tags to guide experimental design and in vivo applications.

Extends targeted degradation beyond small molecules by combining degrader payloads with antibody delivery.

DACs targeting CD71 and Trop-2 delivered dual SMARCA2/4 degrader payloads with controlled release of a VHL degrader.

Expands degradation beyond intracellular targets and opens new therapeutic opportunities.

Development of extracellular targeted protein degradation strategies for proteins traditionally inaccessible to intracellular degraders.

Provides fundamental insight into the biology underlying native CRBN degrons and neosubstrate recognition.

Identification of PCMT1 as an enzyme responsible for generating cyclic imide degrons on endogenous CRBN substrates.

Shows that degradation outcomes can extend beyond the intended target and depend strongly on protein-complex context.

Characterization of collateral degradation events affecting proteins associated with the primary target.

Challenges the paradigm of one glue-one ligase by demonstrating recruitment of multiple degradation effectors.

Monovalent molecular glues recruit both FBXO22 and DCAF16 to degrade SMARCA2/4.

Demonstrates the therapeutic potential of selective EP300 degradation across multiple blood cancers.

CRBN-based EP300 degraders showed strong efficacy while maintaining selectivity.

Demonstrates that molecular glues can create therapeutic benefit by stabilizing protein interactions without inducing degradation.

Development of non-degrading molecular glues that strengthen a weak interaction between mutant CRAF and 14-3-3.

Further establishes FBXO22 as a robust and versatile ligase for targeted protein degradation.

Discovery of a TEAD-FBXO22 molecular glue degrader that drives efficient target degradation.

Expands the repertoire of ligases available for targeted protein degradation.

Modified degron-based recruiters enabled degradation of multiple targets through FBXO31 recruitment.

One of the most important clinical updates in targeted protein degradation and a major step toward tackling mutant KRAS-driven cancers.

Clinical and translational characterization of the KRAS G12D degrader Setidegrasib demonstrates promising activity in patients.

Highlights the growing field of molecular glues that alter protein function through stabilization rather than degradation.

Perspective article examining how molecular glues can modulate protein-protein interactions without triggering target degradation.

Better understanding of oral bioavailability is essential for expanding the reach of degrader therapeutics.

Investigates how chameleonicity and efflux influence oral exposure and provides guidance for degrader optimization.

CNS delivery remains a major challenge for degrader therapeutics and a critical area for future innovation.

Comprehensive review of degraders that have demonstrated activity in the central nervous system.

Expands degradation approaches to extracellular targets traditionally inaccessible to intracellular degraders.

SORTACs leverage sortilin-mediated lysosomal trafficking for extracellular target depletion.

Provides one of the most comprehensive resources available for E3 ligase biology and degrader discovery.

Systematic curation and annotation of the human E3 ligase landscape.

Demonstrates that kinases can act as functional effectors in proximity-based systems, expanding induced proximity beyond E3 ligases.

Recruitment of CSNK1 proteins enables regulation of β-catenin levels through induced proximity.

Demonstrates a new route to targeted degradation that exploits a native protein interaction rather than traditional bifunctional degrader design.

A pseudo-natural product both inhibits IDO1 and promotes interaction with KLHDC3, driving degradation.

Provides medicinal chemistry insights for improving VHL degrader performance.

Removal of a triazole motif significantly improved properties of NAMPT degraders.

Reveals a new mechanism for modulating CRBN activity and substrate specificity.

Identification of an allosteric CRBN binder that alters CRBN conformation and degradation behavior.

Demonstrates selective degradation of BCL6 while avoiding unwanted CRBN neosubstrate degradation.

Development of a potent BCL6 bifunctional degrader with strong efficacy in hematologic cancer models.

Solubility and formulation remain major barriers for many degrader programs.

Development of screening and characterization approaches to identify formulations suitable for bifunctional compounds.

Enhances understanding of DDB1-dependent molecular glue mechanisms.

SAR studies identified determinants of Cyclin K degradation by CDK12-directed molecular glues.

Faster discovery workflows are essential for exploring larger degrader chemical spaces.

Combines click chemistry and D2B approaches to rapidly triage candidate degraders.

Shows how molecular glues can reinforce native protein interactions as an alternative to degradation.

Rationally designed molecular glues stabilized the endogenous interaction between CRAF and 14-3-3 proteins.

Introduces a new modality for target inactivation through induced oligomerization rather than degradation.

PINCHs force proteins such as BCL6 and Keap1 into inactive higher-order assemblies.

Demonstrates a creative strategy for expanding degrader biology through native degron engineering.

Rational modification of a native degron sequence generated a recruiter capable of engaging FBXO31.

Highlights the opportunity to leverage allosteric binders as alternatives to traditional orthosteric starting points.

Review of degrader design strategies originating from allosteric ligands and their unique advantages.

Demonstrates that alternative ligases beyond CRBN and VHL can support efficient targeted degradation.

TEAD degraders utilizing members of the IAP family achieved selective target degradation.

Reveals the breadth and context dependence of CRBN-mediated protein interactions across cell types.

Affinity pulldowns and mass spectrometry were used to define the CRBN glue-able interactome.

Demonstrates degradation of one of the most challenging target classes in drug discovery.

A CRBN-based degrader induced lysosomal degradation of a GPCR.

Provides a framework for understanding how ligand binding influences CRBN conformational states and degradation activity.

Combines biophysics, mutagenesis, and SAR to characterize open and closed forms of CRBN.

Provides a framework for moving molecular glue discovery from empirical observations toward intentional design.

Review of mechanisms and emerging strategies for rational molecular glue discovery across stabilizing and degrading applications.

Illustrates how covalent chemistry can unexpectedly create new proximity-driven biology and transcriptional outcomes.

Covalent BCL6 ligands recruit BRD9 and generate TCIP-like modulation of chromatin-associated targets.

Provides a practical overview of how the field has successfully translated degraders into the clinic.

Reviews major milestones, successes, and remaining challenges in PROTAC drug discovery and development.

Demonstrates that transmembrane ER proteins can be efficiently degraded and reveals unique higher-order ternary complex architecture.

Structural studies show a dimerization-driven 2:2:2 ternary complex underlying IRE1 degradation.

Safety is one of the most important factors determining whether degraders successfully reach patients.

Mechanistic investigation of unexpected toxicity associated with a heterobifunctional degrader provides valuable insights for future degrader design and risk assessment.

Expands induced proximity into glycosylation biology and targeted post-translational modification control.

OGT recruitment is used to selectively modify protein targets through O-GlcNAcylation.

Demonstrates how nanoparticle delivery can enhance degrader delivery and drug loading.

nanoPROTACs were used to increase delivery and exposure of targeted protein degraders.

Expands the biophysical toolkit available for understanding degrader mechanism and ternary complex formation.

Demonstrates use of native MS to characterize PROTAC-induced and CRL-associated protein complexes.

Highlights the potential value of tissue-restricted ligases for achieving selective target degradation.

Development of degraders utilizing MAGEA11, an E3 ligase with restricted expression across cell types.

Demonstrates how covalent induced proximity systems can both create and systematically identify new protein interactions.

Combines dual covalent warheads with deconvolution methods to characterize proximity-induced protein interactions.