Rapid Two-Step Multicomponent Synthesis and Structure-degradation Relationships of Selective HDAC6 PROTAC Degraders.

A 2-in-1 Strategy for the Discovery of Compact HDAC8 Protac Degraders

A “2-in-1” PROTAC design strategy for developing more compact HDAC8 degraders by integrating the CRBN-recruiting ligand into the capping group of an HDAC8 warhead, thereby enabling a single structural motif to engage both HDAC8 and CRBN.

Structure-Guided Development of Selective HDAC4 and HDAC7 Inhibitors That Modulate Th17 Cell Transcription.

Class IIa histone deacetylases (HDACs) are attractive therapeutic targets due to their specialized regulatory functions and restricted expression patterns. Recent studies identified HDAC4 and HDAC7 as critical regulators of Th17-cell differentiation, acting through distinct transcriptional mechanisms to promote Th17 li...

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 a Potent and Selective KRAS G12D Degrader based on PROTAC Degradation.

This work designed and synthesized 20 novel KRAS G12D PROTACs based on the MRTX1133 derivative and found that compound VI-1 exhibited significant KRAS G12D degradation activity in PANC-0203 cells, achieving 69% effective degradation at 10 μM.

Direct-to-Biology Strategy Accelerates CRBN-Targeting 1 Molecular Glue Degrader Discovery

Structure-Based Discovery of Trifluoromethyl Oxadiazole Oxime Ethers as Potent Histone Deacetylase Inhibitors.

TFMO-oxime ethers are identified as promising scaffolds for HDAC-targeted fungicide discovery in Pseudomonas aeruginosa HDAC, and most derivatives showed potent inhibitory activity against Pa-HDAC.