Protein Degradation and Inhibitors

P-NADs: PUX-based NAnobody Degraders for Ubiquitin-Independent Degradation of Target Proteins

This paper introduces P-NADs, a ubiquitin-independent protein degradation method using PUX-adaptor proteins and nanobodies, demonstrating their efficacy in human cells and potential for therapeutic applications.

Unveiling the Power of PROTAC Valency: Navigating Cell Type-Specific Hook Effects

The paper evaluates the impact of PROTAC valency on hook effects, showing that trivalent PROTACs do not eliminate the hook effect but may alter its dynamics.

Welding PROxAb Shuttles: A modular approach for generating bispecific antibodies via site-specific protein-protein conjugation

The paper describes a modular method to generate PROxAb Shuttles by conjugating PROTAC-binding VHHs to antibodies, enabling targeted protein degradation and bispecific antibody creation.

A chemical probe to modulate human GID4 Pro/N-degron interactions

The paper introduces PFI-7, a chemical probe that inhibits GID4 Pro/N-degron interactions, revealing non-degradative roles of the CTLH complex in human cells.

Structural Basis of Conformational Dynamics in the PROTAC-Induced Protein Degradation

The paper analyzes conformational dynamics in PROTAC-induced protein degradation using crystal structures and mathematical modeling, finding that ternary complex rigidity does not enhance degradation and that salt bridges may improve efficiency.

Directed Evolution of Genetically Encoded LYTACs for Cell-Mediated Delivery

The paper describes the development of genetically encodable LYTACs (GELYTACs) for targeted protein degradation using engineered T-cells, showing efficacy in secreting and delivering the therapeutics.

PROTACable is an Integrative Computational Pipeline of 3-D Modeling and Deep Learning to Automate the De Novo Design of PROTACs

PROTACable automates PROTAC design using 3-D modeling and deep learning to predict activity of newly designed PROTACs.

Structure-guided design and optimization of covalent VHL-targeted sulfonyl fluoride PROTACs

This study designs and optimizes covalent VHL-targeted sulfonyl fluoride PROTACs that degrade BRD4 and androgen receptor without linker optimization.

Single-Domain Antibody-Based Protein Degrader for Synucleinopathies

This paper develops a single-domain antibody-based protein degrader that enhances proteasomal and lysosomal degradation of α-synuclein in synucleinopathy models.

Targeted protein degradation systems to enhance Wnt signaling

The paper describes the development of new antibodies that enhance Wnt signaling through targeted protein degradation by sequestering E3 ligases.

Catalytic-independent functions of INTAC in conferring sensitivity to BET inhibition

The paper identifies that BET inhibitor efficacy depends on the INTAC complex's auxiliary module, which interacts with the RACK7/ZMYND8-KDM5C complex to remove H3K4 methylation, thereby restoring sensitivity to BET inhibitors through WDR5 degradation.

Induced degradation of SNAP-fusion proteins

This paper develops SNAP-PROTACs to induce degradation of SNAP-fusion proteins, enabling selective depletion and functional analysis of target proteins.

The CDK12 inhibitor SR-4835 functions as a molecular glue that promotes cyclin K degradation in melanoma

This study identifies SR-4835 as a CDK12 inhibitor that promotes cyclin K degradation via the proteasome by recruiting the CDK12-cyclin K complex to the CUL4-RBX1-DDB1 ubiquitin ligase complex.

Harnessing PROTAC technology to combat stress hormone receptor activation

This paper introduces a novel GR degrader, KH-103, which selectively degrades glucocorticoid receptors and shows improved efficacy over existing inhibitors.

IGF2 Peptide-Based LYTACs for Targeted Degradation of Extracellular and Transmembrane Proteins

This paper develops IGF2-based LYTACs for lysosomal degradation of extracellular and transmembrane proteins, showing enhanced in vitro effects compared to anti-PD-L1 antibodies.

The BET inhibitors JQ1, AZD5153, and I-BET151 co-opt ubiquitin proteasome system components for altering expression of the BRD4 interactome in a human B cell line.

This study identifies how BET inhibitors alter the BRD4 interactome via the ubiquitin proteasome system, revealing complex mechanisms and potential new therapeutic strategies.

Rational Prediction of PROTAC-compatible Protein-Protein Interfaces by Molecular Docking

The paper presents a computational method to predict PROTAC-compatible protein-protein interfaces using docking and scoring techniques, achieving high accuracy in benchmark tests.

Benchmarking PROTAC docking and virtual screening tools

This paper benchmarks PROTAC docking and virtual screening tools to evaluate their ability to predict ternary complexes and distinguish active from inactive PROTACs.

Designed Endocytosis-Triggering Proteins mediate Targeted Degradation and amplify signaling

The paper designs EndoTags to trigger endocytosis and degradation of target proteins, enabling tissue-specific targeting and therapeutic applications.

Elucidation of Genome-wide Understudied Proteins targeted by PROTAC-induced degradation using Interpretable Machine Learning

The paper develops PrePROTAC, an interpretable machine learning model to predict PROTAC-induced protein degradation targets, identifying over 600 novel understudied proteins and proposing PROTAC compounds for Alzheimer's disease targets.

Chemically Induced Degradation of Native Proteins by Direct Recruitment to the 26S Proteasome

This study demonstrates a method to degrade native proteins by directly recruiting them to the proteasome without requiring ubiquitylation.

Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization

This paper develops cell-based assays to monitor PROTAC degradation kinetics and ternary complex formation, revealing that ternary complex stability is critical for PROTAC efficiency.

PROTAC-Design-Evaluator (PRODE) -- An Advanced Method for in-silico PROTAC design

This paper introduces a computational method for in-silico PROTAC design and evaluation, demonstrating its ability to predict PROTAC binding modes and thermodynamics for known and novel target systems.

A ubiquitination-mediated degradation system to target phospho-14-3-3-binding-motif embedded proteins

This paper introduces a method to degrade phospho-14-3-3-binding-motif proteins using a ubiquitin-proteasome system, demonstrating its efficiency and specificity for studying these proteins.

Rapid-kinetics degron benchmarking reveals off-target activities and mixed agonism-antagonism of MYB inhibitors

The paper benchmarks six MYB inhibitors using a nascent transcriptomics assay, revealing partial specificity, off-target activity, and mixed agonism-antagonism effects.

A novel HERC4-dependent glue degrader targeting STING

This paper identifies AK59 as a molecular glue degrader for STING, showing HERC4 is the key E3 ligase for its degradation and demonstrating efficacy against STING mutations.

E3-specific degrader discovery by dynamic tracing of substrate receptor abundance

This paper develops a scalable method to identify E3-specific degraders by tracing substrate receptor abundance changes induced by pharmacological auto-degradation.

Mapping the Energy Landscape of PROTAC-Mediated Protein-protein Interactions

The paper develops a method to restrict the search space for PROTAC-mediated protein-protein interactions using a cyclic coordinate descent algorithm, showing the global minimum corresponds to native-like conformations.

Charting functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders

The paper identifies functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders using haploid genetics and deep mutational scanning.

An in-silico approach for novel molecular glue design by rationalizing known molecular glue mediated ternary complex formation

This paper establishes an in-silico rationale for molecular glue design by analyzing a known case and discusses its application in designing novel molecular glues using AI techniques.