Proteolytic targeting chimeras (PROTACs) are heterobifunctional small molecules consisting of an E3 ligase recruiting molecule and a target protein ligand, tethered by chemical linkers. There are more than 600 E3 ligases in the human proteome, but only a few ligases are currently being used for targeted protein degradation, such as Cereblon (CRBN), Von Hippel Lindau (VHL), MDM2, and IAPs. While CRBN and VHL have shown broad applicability for PROTAC applications, the lack of tractable ligands for novel E3 ligases and the lack of reliable screening methods limit the expansion of PROTACs to new E3 ligases. Despite the great success of traditional drug targets (such as kinases) and “undruggable” targets (such as RAS family proteins), there are still many targets that remain elusive and do not benefit from PROTACs. Lifesensors has developed a suite of assays that can screen for novel ligands and design PROTACs recruiting novel ligases and aid in the discovery of a new generation of PROTACs. Currently, LifeSensors has a library of ~30 ligases that can be explored for PROTAC applications based on target protein compartmentalization and tissue specificity for efficient degradation.
Our Novel E3 ligases for PROTAC service include High-throughput screening for identifying novel ligands, characterizing ligand affinity to novel E3 ligase, demonstrating selectivity, PROTAC design, and evaluating target degradation.
- E3 Ligase Ligand Identification and Validation
- PROTAC® Design & Productive Ternary Complex
- PROTAC® Mediated Target Ubiquitination
- Degradation Assays
E3 Ubiquitin Ligases
Hundreds of E3 ligases have been identified in mammalian ubiquitylation cascades. E3 ligases conjugate monoubiquitin or polyubiquitin with various chain architectures to protein substrates or themselves.
Technology to specifically isolate polyubiquitylated proteins from cell lysates and tissues using Tandem Ubiquitin Binding Entities (TUBEs).