Discovery of Stapled Peptide MYC Degrader with Potent In Vivo Activities for Triple-Negative Breast Cancer Therapy.

Harnessing the E3 Ligase KLHL12 for Tumor-Selective Protein Degradation.

KLHL12 is identified as a potentially tumor-selective E3 ligase and the development of the first-in-class KLHL12-recruiting PROTACs are reported, which established KLHL12 as a promising tumor‑selective E3 ligase and provided a KLHL12-recruiting PROTAC platform for cancer therapy.

Discovery of rigid linker-based CDK4/6 PROTACs for the treatment of breast cancer.

A series of novel CDK4/6 PROTACs based on dalpiciclib incorporating rigid linkers showed potential to overcome acquired resistance to CDK4/6 inhibitors, demonstrating stronger anti-breast cancer activity than dalpiciclib both in vitro and in vivo.

Novel VHL ligand-based PROTACs targeting JNK1: design, synthesis, and biological evaluation with potent anti-EMT activity.

This work describes the design, synthesis, and biological evaluation of a series of JNK1-targeting PROTACs that recruit either CRBN or VHL E3 ligases that demonstrates excellent degradation potency and selectivity for JNK1, highlighting its potential as a valuable chemical probe for EMT-associated pathologies.

Design, synthesis, and biological characterization of a hydrophobic tagging EGFR degrader for the treatment of non-small-cell lung cancer.

Structure-Guided Optimization of p62-Directed AUTOTACs for Efficient EGFR/VEGFR2 Degradation and Antitumor Efficacy.

Receptor tyrosine kinases (RTKs) are core cancer therapeutic targets, yet their integral membrane localization hinders efficient degradation by traditional ubiquitin-proteasome system (UPS)-based targeted protein degradation (TPD) strategies. Herein, we describe the structure-guided development of p62/SQSTM1-directed a...

Combinatorial screening of biological degrader modules identifies heterobifunctional molecules that efficiently destroy MYC, leading to rapid tumour cell death in vitro and in vivo

Targeted protein degradation is a potent strategy against intracellular proteins impervious to traditional drugs. We describe a platform reliant on high-throughput cloning and mRNA-based delivery to quickly screen 100s-1000s of modular biological degraders, which we challenge against the high-turnover c-Myc oncoprotein...