LYTACs and other extracellular targeted protein degradation TACnologies: guiding principles and potential clinical prospects
Abstract
Lysosome-targeting chimeras (LYTACs) have emerged as a powerful modality in the field of extracellular targeted protein degradation (eTPD). The proximity-inducing mode of action of LYTACs can be applied to a growing number of lysosome-targeting receptors (LTRs) and membrane-bound E3 ligases to degrade extracellular proteins. In this review, we highlight preceding eTPD approaches and discuss in depth the plethora of newly identified LTRs that can be exploited in a LYTAC molecule. To provide guidance in the fast-growing LYTAC field, we elaborate on parameters to assess the preclinical validation of the various TACnologies, highlight opportunities for engineering catalytic LYTACs, and finish with pharmacokinetic (PK) considerations.
Fields of Study & Subjects
Protein Degradation and Inhibitors
Click Chemistry and Applications
Ubiquitin and proteasome pathways
Publication details
- Journal / source
- Drug Discovery Today
- Publisher
- Elsevier BV
- Volume
- 31
- Issue
- 2
- Pages
- 104601–104601
- Publication date
- 12 January 2026
- Language
- EN